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Noted This Week - 2018 Archive

Archive of cancer-related news briefs, by week, for 2018

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December 2018

December 21, 2018–January 3, 2019

Bristol-Myers Squibb (BMS) will acquire Celgene for $74 billion. Celgene’s leading drug is the immunomodulatory agent lenalidomide (Revlimid), whereas BMS is known for its PD-1 inhibitor nivolumab (Opdivo) and its CTLA4 inhibitor ipilimumab (Yervoy), although it also makes many other types of drugs. Last year, Celgene acquired Juno Therapeutics for $9 billion and bought Impact Biomedicines for $1.1 billion.
The FDA approved dasatinib (Sprycel) in combination with chemotherapy as a first-line therapy for children age 1 and older with Philadelphia chromosome–positive acute lymphoblastic leukemia. The approval was based on a phase II trial in which all 78 patients treated with the drug achieved a complete remission; the 3-year event-free survival rate was 64.1%. Dasatinib was previously approved for certain forms of chronic myeloid leukemia.
The agency also approved tagraxofusp-erzs (Elzonris; Stemline Therapeutics) for blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and children age 2 and older. The approval was based on a phase I trial in which the drug elicited responses in seven of 13 patients at a median follow-up of 11.5 months. Tagraxofusp-erzs, a CD123-directed cytotoxin, is the first drug approved for BPCDN, and the first approved therapy targeting CD123.
The FDA is one of the agencies affected by the ongoing partial government shutdown. During the shutdown, the FDA cannot accept new drug and device applications if user fees have not already been paid, and the Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research have stopped performing certain tasks such as nonemergency analysis of blood and tissue samples. However, the agency will continue critical public health activities, such as addressing flu and foodborne illness outbreaks, supporting high-risk food and medical product recalls, and pursuing civil and criminal investigations.

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A study in JAMA Oncology established that microsatellite instability–high/mismatch repair–deficient (MSI-H/dMMR) prostate cancer is uncommon, yet these genomic instabilities may be therapeutically important. Researchers analyzed data from 1,033 patients and found that although only 32 (3.1%) had MSI-H/dMMR prostate cancer, six of 11 patients with the instabilities who received anti–PD-1/PD-L1 therapy exhibited a response. Additionally, 21.9% of patients with MSI-H/dMMR disease had a germline mutation in an MMR gene.
Being overweight accounts for cancer in at least one of every 17 cases in the United States, according to findings published in JAMA Oncology. Researchers conducted a large-scale analysis of adults and found that the proportion of cancers that could be attributed to excess body weight ranges from 3.9% to 6% for men and 7.1% to 11.4% for women, with the highest rates for men in Texas and women in the District of Columbia.

December 14–20

The FDA approved trastuzumab-pkrb (Herzuma; Celltrion), a biosimilar of trastuzumab (Herceptin; Genentech) for HER2-positive metastatic breast cancer. Trastuzumab-dkst (Ogivri; Mylan), another biosimilar of trastuzumab, was previously approved by the FDA for certain forms of HER2-positive breast and stomach cancers.
The agency also approved the PARP inhibitor olaparib (Lynparza; AstraZeneca) as a maintenance therapy for patients with certain BRCA-mutated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancers following chemotherapy. The approval was based on the phase III SOLO-1 trial, in which median progression-free survival (PFS) was not reached among those who received the drug, compared with 13.8 months among patients who received a placebo. The agency also approved the BRACAnalysis CDx (Myriad) as a companion diagnostic.
The FDA granted an accelerated approval to pembrolizumab (Keytruda; Merck) for adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma. In the phase II KEYNOTE-017 trial, 50 patients treated with the drug had an overall response rate of 56%, and had not reached the median duration of response at a median follow-up of 14.9 months. A PD-1 inhibitor, pembrolizumab is already approved for the treatment of several malignancies, including cervical and gastric cancers and melanoma.
The FDA issued a warning about differentiation syndrome in patients receiving enasidenib (Idhifa; Celgene and Agios) or ivosidenib (Tibsovo; Agios), two IDH inhibitors recently approved for acute myeloid leukemia. The side effect, which can be associated with dyspnea, acute kidney failure, and various other nonspecific symptoms, occurs in approximately 20% of patients treated with the drugs, and more than half of the cases are classified as grade 3 or worse, according to an analysis presented earlier this month at the 2018 American Society of Hematology Annual Meeting in San Diego, CA.

Researchers concluded that three biomarkers, individually and/or combined, may identify patients likely to respond to pembrolizumab, according to a study in the Journal of Clinical Oncology. Researchers analyzed data from the phase Ib KEYNOTE-028 trial of 475 patients with PD-L1–positive advanced solid cancers who were treated with the PD-1 inhibitor. They found that those with a higher T cell–inflamed gene expression profile (GEP), PD-L1 expression, and/or tumor mutational burden (TMB) had higher response rates and longer PFS; those with high levels of both inflammatory markers (GEP or PD-L1) and TMB were the most likely to respond.
U.S. Surgeon General Jerome Adams, MD, released an advisory about electronic cigarette (e-cigarette) use among youths. He declared the uptake of e-cigarettes among children "an epidemic," and described the potential harms of using the devices. He also called for more aggressive steps to prevent youth access, outlining actions that can be taken by parents, teachers, health professionals, and state and local governments.
The multikinase inhibitor sorafenib (Nexavar; Bayer and Onyx) may improve outcomes of patients with desmoid tumors, according to findings published in The New England Journal of Medicine. In a phase III trial of 87 patients with progressive, symptomatic, or recurrent tumors, those treated with the drug had an overall response rate of 33% and a 2-year PFS of 81%, compared with 20% and 36%, respectively, in those who received a placebo.

December 7–13

A new framework outlines how the FDA plans to incorporate real-world evidence (RWE) into the drug review process. Per the framework, the agency will consider RWE for the approval of new indications for already-approved drugs, and to satisfy post-approval study requirements. The FDA will use a three-part approach, which includes steps like assessing real-world data and the studies that generated them, when determining whether RWE is appropriate to answer a regulatory question.
In a paper in Science, researchers identified molecular features of glioblastoma that are associated with specific clinical outcomes. Researchers performed genomic sequencing on 416 neuroblastoma tumors and assessed telomere maintenance mechanisms in 208 of the tumors. They found that low-risk tumors lacked telomere maintenance mechanisms, whereas intermediate-risk tumors had the maintenance mechanisms, and high-risk tumors had the maintenance mechanisms plus RAS and/or p53 pathway mutations.
MacroGenics announced that the FDA ordered a partial clinical hold on MGD009, a bispecific Dual-Affinity Re-Targeting molecule that targets B7-H3 and CD3. The hold came after the company reported liver-related side effects in a phase I trial testing the drug as a monotherapy in patients with various solid tumors. The company will halt enrollment in this trial and another phase I trial testing the drug in combination with the experimental anti–PD-1 therapy MGA012.
The FDA granted an orphan drug designation to M7824 (EMD Serono) for biliary tract cancer. In a phase I trial, 30 patients treated with the drug after their cancer worsened on platinum-based first-line therapy had an overall response rate of 20%, with responses ranging from 8.3 to more than 13.9 months. M7824 is an experimental bifunctional immunotherapy that combines an anti–PD-L1 mechanism with a TGFβ trap.

Roche announced that it will develop a pan-cancer companion diagnostic to detect mismatch repair deficiency in solid tumors. The test will be used to identify adult and pediatric patients with inoperable or metastatic solid tumors who may benefit from Merck’s anti–PD-1 therapy pembrolizumab (Keytruda), which was the first drug FDA approved based on a common biomarker rather than tumor type.
The debate over the use of fetal tissue in research continued at a meeting of the NIH’s Advisory Committee to the Director, during which NIH director Francis Collins, MD, PhD, said that although the agency will spend up to $20 million on research alternatives, "there is strong evidence that scientific benefits can come from fetal tissue research, which can be done with an ethical framework." Meanwhile, the NIH announced that the government-mandated freeze on fetal tissue procurement put in place in September may soon impede cancer research in at least one lab at the NCI.
Cancer Research UK and AstraZeneca announced the launch of the Joint Cancer Research UK–AstraZeneca Functional Genomics Center, to be located at the University of Cambridge in the UK. Research at the center will focus on how technologies such as CRISPR can be used to advance research on cancer genetics, and to identify and test potential drug targets.

November 30–December 6

Substituting adjuvant trastuzumab emtansine (T-DM1; Kadcyla; Genentech) for trastuzumab (Herceptin; Genentech) may improve outcomes for patients with early-stage HER2-positive breast cancer who have residual disease after treatment, according to findings presented at the 2018 San Antonio Breast Cancer Symposium in Texas, and simultaneously published. In the phase III KATHERINE trial, 12.2% of patients treated with T-DM1 developed invasive disease or died, whereas 88.3% had not developed invasive disease at 3 years, compared with 22.2% and 77%, respectively, of those receiving trastuzumab. T-DM1, a conjugate of trastuzumab and the anticancer drug DM1, is FDA approved for metastatic HER2-positive breast cancer.
NCI Director Ned Sharpless, MD, spoke about the importance of big data in cancer research at the 2018 American Society of Hematology (ASH) Annual Meeting in San Diego, CA. For the NCI, "the overarching goal is to create large, linked, multimodal databases that have histology and radiology and genetics and clinical outcomes, and … make them available to the research community in the most useful format possible," he said.
The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel (Kymriah; Novartis) elicits lasting responses in patients with relapsed/refractory leukemia and lymphoma, according to updated results of two phase II trials presented at the ASH Annual Meeting. In the ELIANA trial, 79 pediatric and young adult patients with acute lymphoblastic leukemia had an overall response rate (ORR) of 82%, and a complete response rate (CRR) of 62%. At 18 months, 66% of the complete responders were still in remission, and the overall survival (OS) rate was 70%; the median OS had not been reached. In the JULIET trial, 115 adult patients with diffuse large B-cell lymphoma had an ORR of 54% and a CRR of 40%, with a median OS of 11.1 months. At 19 months, the median duration of response had not been reached.
Also at the ASH Annual Meeting, Amgen presented positive phase I clinical data for AMG 420, a novel bispecific T-cell engager that targets BCMA. In the trial, 42 patients with relapsed/refractory multiple myeloma were treated with varying doses of the drug. In total, 13 responded, with seven complete responses, and 48% of patients experienced serious side effects; the second-highest dose (400 µg/day) elicited responses in seven out of ten patients, with six still responding at 7.5 months. AMG 420 has been granted a fast track designation by the FDA.

"We're living in an extraordinary period of innovation, particularly in this domain of CAR T-cell therapeutics, yet there are some challenges ahead [in terms of] how these T-cell therapeutics get paid for," said Joseph Alvarnas MD, of the City of Hope Comprehensive Cancer Center in Duarte, CA, while moderating a session on CAR T-cell therapies at the ASH Annual Meeting. During the session, researchers discussed their reimbursement experiences with the therapies, including difficulties they’ve encountered with Medicare payment.
GlaxoSmithKline finalized a deal to acquire Tesaro for $5.1 billion. Tesaro’s lead drug is the PARP inhibitor niraparib (Zejula) that was FDA approved in 2017 as a maintenance therapy for women with recurrent ovarian, fallopian tube, or primary peritoneal cancers, and is now being tested in lung, breast, and prostate cancers. Tesaro is also developing other anticancer drugs, including PD-1, TIM3, and LAG3 inhibitors.
Genentech announced that the FDA approved the PD-1 inhibitor atezolizumab (Tecentriq) in combination with bevacizumab (Avastin) and chemotherapy as a first-line treatment for patients with metastatic nonsquamous non–small cell lung cancer who do not have EGFR/ALK mutations. The approval is based on the phase III IMpower150 trial, in which patients treated with the combination had a median progression-free survival of 8.5 months and a median OS of 19.2 months, compared with 7 months and 14.7 months, respectively, in patients who received bevacizumab and chemotherapy.
AbbVie will halt enrollment of a phase III trial of rovalpituzumab tesirine (Rova-T), an antibody–drug conjugate being tested as a second-line therapy for advanced small cell lung cancer. The decision was based on the TAHOE trial, in which patients treated with the drug had a shorter OS than patients who received standard topotecan chemotherapy.

November 2018

November 21–29

The FDA has been busy the past 10 days, approving several new drugs and expanding the list of indications for others:
- The first TRK inhibitor, larotrectinib (Vitrakvi; Loxo Oncology) was approved for patients of all ages who have solid tumors harboring fusions in NTRK1, NTRK2, or NTRK3, irrespective of tissue of origin. This is the second time that the FDA has granted marketing authorization based on a common molecular marker—pembrolizumab (Keytruda; Merck) received the first tissue-agnostic approval. However, this is the first time that the agency had done so for a targeted therapy and the first time that a drug’s initial approval hasn’t been based on tumor site.
- Celltrion’s rituximab-abbs (Truxima) became the first biosimilar to Rituxan (rituximab)—and the first in the United States—to treat non-Hodgkin lymphoma (NHL). It can be used as a single agent or in combination with chemotherapy to treat adults with CD20-positive, B-cell NHL.
- Gilteritinib (Xospata; Astellas) was approved to treat adults with FLT3 mutation–positive relapsed or refractory acute myeloid leukemia (AML). The agency also approved the LeukoStrat CDx FLT3 Mutation Assay (Invivoscribe Technologies) to detect FLT3 mutations. The approval was based on data from the ADMIRAL study, in which the rate of complete remission (CR) or CR with partial hematologic recovery among 138 patients was 21% at a median follow-up of 4.6 months.
- For adults age 75 or older who cannot tolerate intensive chemotherapy, the FDA granted marketing authorization to glasdegib (Daurismo; Pfizer), to be used in combination with low-dose cytarabine (LDAC), to treat newly-diagnosed AML. Glasdegib is a small molecule inhibitor of the Sonic hedgehog pathway, which is overexpressed in many types of cancer.

Also for patients age 75 or older newly diagnosed with AML, venetoclax (Venclexta; Genentech, AbbVie) was greenlighted as a first-line therapy. Under the approval, venetoclax will be used in combination with azacitidine, decitabine, or LDAC. The drug, a Bcl-2 inhibitor, was previously approved as a second-line therapy for chronic lymphocytic leukemia and small cell leukemia.
Researchers identified the transcription factor ONECUT2 (OC2) in prostate tumors. In metastatic castration-resistant prostate cancer (mCRPC), OC2 works as a master regulator of androgen receptor networks and activates genes linked to neural differentiation and disease progression. In additional experiments using human tissue and mouse models, the investigators identified a compound, CSRM617, that counteracted OC2. OC2 “may be an important therapeutic target in as many as one third of mCPRC tumors,” the researchers wrote.
For some women, mammography screening starting at age 30 could be beneficial, according to research presented at the Radiological Society of North America’s annual meeting in Chicago, IL. Researchers analyzed more than 5.7 mammograms performed on more than 2.6 million women at 150 facilities over 8 years. They found that, compared with women ages 40 to 44 at average risk, screening women younger than 40 with dense breasts or a personal or family history of breast cancer yielded similar rates of cancer detection and recall for suspicious findings.
Bristol-Myers Squibb announced that the CheckMate-451 study did not meet its primary endpoint of overall survival. The phase III trial was evaluating the PD-1 inhibitor nivolumab (Opdivo) in combination with the CTLA1 inhibitor ipilimumab (Yervoy) versus placebo as a maintenance therapy for patients with extensive-stage small cell lung cancer (SCLC) without disease progression after completion of first-line.

November 16–20

The FDA approved brentuximab vedotin (Adcetris; Seattle Genetics) in combination with chemotherapy as a first-line therapy for systemic anaplastic large-cell lymphoma or other CD30-expressing peripheral T-cell lymphomas. The approval was based on the ECHELON-2 trial, in which patients treated with the drug had a median progression-free survival (PFS) of 48.2 months, compared with 20.8 months in patients who received chemotherapy alone. The drug, an antibody–drug conjugate, was the first approved through the FDA’s Real-Time Oncology Review Pilot Program.
Boston Scientific announced it will acquire British-based BTG for $4.2 billion. BTG specializes in medical devices that are used as interventional therapies. It has developed radiotherapy microspheres and a cryoablation system to treat patients with kidney, liver, and other cancers.
The UK’s National Institute for Health and Care Excellence (NICE) recommended tisagenlecleucel (Kymriah; Novartis) for patients under age 25 with relapsed/refractory B-cell acute lymphoblastic leukemia. National Health Service England will make the drug available to patients via the Cancer Drugs Fund. The drug, which was previously approved in Europe, had not been backed by NICE due to cost, and is still not recommended for patients 25 and older.
AstraZeneca’s PD-L1 inhibitor durvalumab (Imfinzi) may not be an effective first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) who have PD-L1 expression in at least 25% of cancer cells. In the phase III MYSTIC trial, the drug, either alone or in combination with the anti-CTLA4 therapy tremelimumab (MedImmune and AstraZeneca) did not significantly extend overall survival (OS) compared with standard chemotherapy. Durvalumab was previously approved as a second-line treatment for urothelial cancer and for NSCLC that has not progressed following concurrent platinum-based chemotherapy and radiation therapy.

EMD Serono announced that the PD-L1 inhibitor avelumab (Bavencio) did not improve outcomes for patients with platinum-resistant/refractory ovarian cancer. In the phase III JAVELIN Ovarian 200 trial, patients treated with the drug, either alone or in combination with pegylated liposomal doxorubicin (PLD), did not have significantly better OS or PFS than patients who received PLD alone.
Only about a third of required pediatric studies on drugs approved for adults are completed, according to findings published in JAMA Pediatrics. Researchers assessed studies in pediatric patients that tested 114 new drugs and new indications approved for adults by the FDA between 2007 and 2014. They found that 33.8% of the 222 pediatric studies required by these approvals were completed, and 45% of completed studies published results. At the time of approval, only 15.8% of drug labels included pediatric information.
Bristol-Myers Squibb announced that the FDA approved the monoclonal antibody elotuzumab (Empliciti) in combination with pomalidomide and dexamethasone for patients with multiple myeloma who have received at least two prior therapies. The approval was based on the phase II ELOQUENT-3 trial, in which patients treated with the drug cocktail had a median progression-free survival of 10.3 months and an overall response rate (ORR) of 53%, compared with 4.7 months and 26% in patients who received pomalidomide and dexamethasone. Elotuzumab was previously approved for the same disease in combination with lenalidomide and dexamethasone.

November 9–15

The FDA announced plans for an antitobacco effort targeting underage use of tobacco products. The agency will restrict sales of flavored electronic cigarette (e-cigarette) cartridges to retail stores that have age-restricted entry or age-restricted areas, and it will require more stringent age verification for online sales. The FDA also proposed bans on menthol in cigarettes and cigars, and other flavors in cigars.
Under pressure from the FDA, Juul Labs said it will stop selling certain flavored e-cigarette cartridges—namely mango, fruit, crème, and cucumber—in 90,000 retail stores, and it will also improve its online age-verification system. The company, which makes e-cigarettes that look like flash drives that are popular with teens, will also halt social media advertising of flavored cartridges.
Merck announced that the FDA approved the PD-1 inhibitor pembrolizumab (Keytruda) for patients with advanced hepatocellular carcinoma who previously received sorafenib (Nexavar; Bayer, Onyx). The approval was based on the phase II KEYNOTE-224 trial, in which 104 patients had an objective response rate of 17%; 89% of those who responded did so for at least 6 months, and 56% responded for at least 12 months. The drug is already approved for several other types of cancer.

Merrimack Pharmaceuticals announced that it will halt development of the anti-HER2 drug MM-121 and lay off 60% of its staff. The decision comes after a phase II trial of the drug in combination with docetaxel showed no improvement in progression-free survival compared with docetaxel alone in patients with non–small cell lung cancer. Merrimack will continue to pursue its anti-EphA2 drug MM-310, which is being tested in a phase I trial for solid tumors.
Boehringer Ingelheim agreed to pay Epizyme $15 million up front plus $5 million in research funding in a deal that could earn Epizyme over $280 million more in milestone payments. Together, the companies will develop cancer therapies for small-molecule targets. For example, they are launching a helicase program that will focus on two novel epigenetic targets in the helicase and histone acetyltransferase families.

November 2–8

Bristol-Myers Squibb announced that the FDA approved the monoclonal antibody elotuzumab (Empliciti) in combination with pomalidomide and dexamethasone for patients with multiple myeloma who have received at least two prior therapies. The approval was based on the phase II ELOQUENT-3 trial, in which patients treated with the drug cocktail had a median progression-free survival of 10.3 months and an overall response rate (ORR) of 53%, compared with 4.7 months and 26% in patients who received pomalidomide and dexamethasone. Elotuzumab was previously approved for the same disease in combination with lenalidomide and dexamethasone.
The agency also granted an accelerated approval to the ALK inhibitor lorlatinib (Lorbrena; Pfizer) for patients with ALK-positive metastatic non–small cell lung cancer (NSCLC) whose disease worsens after other therapies. Approval was based on a phase I/II trial in which 215 patients had an ORR of 48% and an estimated median duration of response of 12.5 months; 89 patients with brain metastases had an ORR of 60%. This is the first FDA approval for lorlatinib.
Coherus BioSciences announced that the FDA approved pegfilgrastim-cbqv (Udenyca), a biosimilar of pegfilgrastim (Neulasta; Amgen). The drug decreases the risk of infection in patients with nonmyeloid cancer who are receiving chemotherapy and have febrile neutropenia. The agency approved pegfilgrastim-jmdb (Fulphila; Mylan), the first biosimilar of pegfilgrastim, in June.

Novartis announced that it will no longer pursue FDA approval of GP2013, a biosimilar of rituximab (Rituxan; Genentech). The decision comes after the FDA declined to approve the CD20 inhibitor in May without additional information. The drug has been approved by the European Commission and in Switzerland, Japan, New Zealand, and Australia for certain forms of non-Hodgkin lymphoma, chronic lymphocytic leukemia, and various immune diseases.
Global melanoma mortality rates are increasing among men but steady or decreasing among women, according to findings presented at the 2018 National Cancer Research Institute Cancer Conference in Glasgow, UK. Researchers analyzed 3-year average death rates in 33 countries between 1985 and 2015 and found that more men than women died from melanoma in all of the countries; In 32 countries, the mortality rate for men increased.
Janssen agreed to pay Yuhan $50 million up-front for the EGFR inhibitor lazertinib in a deal that could earn the South Korea–based company up to $1.25 billion in milestone payments. The drug is being developed as a therapy for EGFR-mutated NSCLC, and it may shrink metastases in the brain. Janssen and Yuhan will collaborate on trials testing lazertinib alone and in combination with other therapies.
Illumina will acquire Pacific Biosciences for $1.2 billion. With the deal, Illumina will add PacBio’s long-read sequencing technology to its own short-read sequencing platforms. The acquisition will also broaden Illumina’s portfolio to include de novo assembly of plant and animal genomes, functional genomics, tissue transplantation, and pharmacogenomics.

October 2018

October 26–November 1

Johnson & Johnson’s patent on abiraterone (Zytiga) was deemed invalid by a federal judge in New Jersey. The patent is for combining the active ingredient of abiraterone—a CYP17 inhibitor approved by the FDA for prostate cancer—with the steroid prednisone. The decision clears the path for generic versions of the drug, which are being developed by multiple companies, including Teva, Amneal, and Hikma.
Roche announced that the European Commission approved the BCL2 inhibitor venetoclax (Venclyxto) in combination with the anti-CD20 antibody rituximab (Rituxan) as a second-line therapy for patients with chronic lymphocytic leukemia. The approval was based on results from the phase III MURANO trial, in which the combination significantly extended progression-free survival (PFS) compared with the combination of bendamustine plus rituximab, a current standard of care.
Merck announced that the FDA approved pembrolizumab (Keytruda) plus chemotherapy as a first-line treatment for metastatic squamous non–small cell lung cancer. The approval was based on results of the phase III KEYNOTE-407 trial, in which patients treated with the combination had a median overall survival of 15.9 months and a median PFS of 6.4 months, compared with 11.3 months and 4.8 months in patients who received chemotherapy alone. A PD-1 inhibitor, pembrolizumab is already approved for various cancers, including cervical, gastric, and other forms of lung cancer.

A novel anti-CD47 drug may be a promising therapy for patients with non-Hodgkin lymphoma, according to a study published in The New England Journal of Medicine (NEJM). In a phase Ib trial, researchers administered the experimental antibody Hu5F9-G4 in combination with rituximab to 22 patients with diffuse large B-cell lymphoma or follicular lymphoma. Fifty percent of patients had an objective response and 36% had a complete response.
Women with early-stage cervical cancer who have open surgery may have better outcomes than those who have minimally invasive hysterectomies, according to a study in NEJM. Researchers assigned 631 women to open surgery or minimally invasive hysterectomy groups and found that 96.5% of those who had open surgery were disease-free at 4.5 years, compared with 86% of those who had a minimally invasive procedure. An epidemiologic study of 1,225 women also published in NEJM had similar findings.
<Some 39% of Americans believe that cancer can be cured with alternative therapies, such as enzyme and oxygen treatments, diet, and vitamins, according to a survey of 4,887 adults—including 1,001 who have or have had cancer. A study published last year found that patients with common cancers who chose alternative therapies were 2.5 times more likely to die than patients who received standard treatment.

October 19–25

Bristol-Myers Squibb’s nivolumab (Opdivo) plus ipilimumab (Yervoy) provides a durable, long-term survival benefit to patients with advanced melanoma, according to data presented at the European Society for Medical Oncology (ESMO) 2018 Congress in Munich, Germany, and published in The Lancet Oncology. In a phase III trial, at a minimum follow-up of 4 years, median overall survival (OS) was not reached in the nivolumab plus ipilimumab group, compared with 36.9 months in the nivolumab group and 19.9 months in the ipilimumab group. The combination received FDA approval for advanced melanoma in 2016.
In more ESMO news, adding radiotherapy to standard treatment improves outcomes for some men with prostate cancer. Published in The Lancet, the phase III STAMPEDE trial found that 81% of men with a low metastatic burden—defined based on the number and location of metastases—who were treated with radiotherapy in addition to standard treatment were alive after 3 years, compared with 73% of men who received standard-of-care treatment alone.
Other findings presented at the ESMO 2018 Congress, and published in The New England Journal of Medicine (NEJM), suggest that the CDK4/6 inhibitor palbociclib (Ibrance; Pfizer) plus fulvestrant extends survival of women with HR-positive, HER2-negative advanced breast cancer whose disease worsened on endocrine therapy. In the phase III PALOMA-3 trial, women treated with the combination had a median OS of 34.9 months, and 49.6% were still alive after 3 years, compared with 28 months and 40.8% in those who received fulvestrant plus a placebo. The combination was FDA approved for this indication in 2016.
Also presented at the ESMO 2018 Congress and published in the NEJM, maintenance therapy with olaparib (Lynparza; AstraZeneca) improves survival of patients with advanced ovarian cancer who have BRCA1/2 mutations. In the phase III SOLO-1 trial, 60.4% of patients treated with the drug were alive after 3 years, compared with 26.9% who received standard treatment. Olaparib, a PARP inhibitor, is approved as a maintenance therapy.

A liquid biopsy test may indicate whether patients with human papillomavirus (HPV)–related oropharyngeal squamous cell carcinoma are cancer free after radiation therapy, according to results presented at the 2018 American Society for Radiation Oncology Annual Meeting in San Antonio, TX. Researchers administered the test, which detects circulating tumor HPV DNA, to 89 patients before, during, and after treatments. Of the 70 patients who tested negative at 3 months, all remained cancer free for an average of 19.8 months.
AstraZeneca agreed to pay Innate $170 million for full ownership of monalizumab, an investigational anti-NKG2A drug for head and neck cancer. AstraZeneca will also gain access to Innate’s experimental anti-CD39 drug IPH5201 and four other drug candidates. Additionally, Innate will pay AstraZeneca $50 million for the right to sell the CD22-directed recombinant immunotoxin moxetumomab pasudotox-tdfk (Lumoxiti), recently approved for hairy-cell leukemia.
NeoGenomics announced it will acquire the clinical oncology laboratory Genoptix for $138.7 million. Genoptix specializes in diagnostic testing for cancers in the bone marrow, blood, and lymph nodes, as well as molecular testing for solid tumors: In September, the company began marketing the BCR–ABL MRDx TFR Monitoring Test for patients with chronic myeloid leukemia being treated with nilotinib (Tasigna; Novartis).
Pennsylvania passed legislation providing for the reimbursement of patients’ expenses related to their participation in cancer clinical trials that aren’t covered as part of the trial, such as travel to and from the trial site. California passed a similar law in 2002.

October 12–18

The FDA approved the PARP inhibitor talazoparib (Talzenna; Pfizer) for patients with advanced or metastatic HER2-negative breast cancer who have BRCA1/2 mutations. The approval was based on results of the phase III EMBRACA trial, in which patients treated with the drug had a median progression-free survival of 8.6 months, compared with 5.6 months in patients who received chemotherapy. The agency also approved the BRACAnalysis CDx test (Myriad Genetics) as a companion diagnostic.
The agency also issued a draft guidance on the use of minimal residual disease (MRD) as a biomarker in clinical trials for blood cancers. The document outlines how MRD might be used in trials, considerations for specific hematologic malignancies, and requirements for drug applications that utilize MRD. The FDA will release a final guidance after addressing any concerns raised during the current 60-day comment period.
Researchers released molecular data from 562 patients with acute myeloid leukemia (AML), reporting their initial findings in Nature. The data, gathered in the Beat AML Master Trial and available to researchers online, includes genomic sequencing results from 672 tumors, as well as assessments of how tumor cells responded to targeted therapies.
Novartis will acquire Endocyte, which develops radiopharmaceuticals, for $2.1 billion. Endocyte’s lead candidate is Lu-PSMA-617, a radioligand being studied in a phase III trial of men with metastatic castration-resistant prostate cancer.
Genomic testing of pediatric patients with cancer can provide clinically useful information, according to findings from the Genomes for Kids study presented at the American Society of Human Genetics 2018 Annual Meeting in San Diego, CA. Researchers sequenced tumors and non-cancerous tissues from 253 patients across cancer types, and determined that 79% of the time, at least one finding could help guide care by providing a diagnosis, revealing patient-specific risks, or identifying drug targets.

Bristol-Myers Squibb announced that in the phase III CheckMate-331 trial, the PD-1 inhibitor nivolumab (Opdivo) did not extend overall survival in patients with small cell lung cancer (SCLC) who relapsed after chemotherapy. The FDA previously granted the drug an accelerated approval for patients with SCLC who have received chemotherapy and at least one other therapy.
Most women diagnosed with ovarian cancer worldwide are unfamiliar with the disease, according to results of the World Ovarian Cancer Coalition Every Woman Study. Researchers surveyed over 1,500 women with ovarian cancer in 44 countries, and found that two thirds had minimal knowledge of the disease before diagnosis, and while nine in ten experienced symptoms prior to diagnosis, less than half consulted a doctor within a month.
The FDA expanded the use of the human papillomavirus (HPV) vaccine Gardasil 9 (Merck) to include individuals up to age 45. The vaccine, which was approved in 2014 for males and females ages 9 to 26, protects against nine different strains of HPV, including seven than can lead to cancer. The expansion was based on new data showing the vaccine is safe and effective in those over 26.

October 5–11

The investigational RET inhibitor BLU-667 may be an effective treatment for patients with advanced RET-altered medullary or papillary thyroid cancers, according to updated results presented at the Annual Meeting of the American Thyroid Association in Washington, DC. In the phase I ARROW trial, 90% of 35 patients with either cancer type had tumor shrinkage regardless of the type of RET alteration or prior treatment with a multikinase inhibitor. Additionally, 62% of patients with medullary thyroid cancer responded to the drug.
Affimed placed a clinical hold on phase I trials of AFM11, an experimental CD19/CD3-targeting T-cell engager. The hold came after one patient died and two patients experienced life-threatening side effects in trials testing the drug in CD19-positive B-cell non-Hodgkin lymphoma and acute lymphoblastic leukemia.
A new clinical guideline supports a shorter course of radiation treatment in men with early-stage prostate cancer. The guideline, issued by the American Society for Radiation Oncology, the American Society of Clinical Oncology, and the American Urological Association, recommends offering 4 to 5 weeks of high-dose hypofractionated external beam radiation therapy (EBRT) as an alternative to 8 to 9 weeks of conventional EBRT. The conclusion is based on evidence from 61 studies, including four large clinical trials.

China approved 17 cancer drugs for inclusion on its national health insurance plan, with pharmaceutical companies offering discounts averaging 56.7%. AstraZeneca will provide a 71% discount for its EGFR inhibitor osimertinib (Tagrisso), whereas Pfizer will offer 70% price cuts for the tyrosine kinase inhibitor axitinib (Inlyta) and the MET inhibitor crizotinib (Xalkori). The new prices will be in effect until November 2020.
Tobacco control is the most important factor for U.S. cancer prevention, according to a report published by the American Cancer Society. Researchers found that a decrease in tobacco smoking was responsible for more than half of the 26% decline in U.S. cancer mortality rates observed since 1991, though smoking is still the most common cause of cancer. Other cancer risk factors included obesity, alcohol, diet, and lack of physical activity.

September 28–October 4

The FDA approved the PD-1 inhibitor cemiplimab (Libtayo; Regeneron) to treat patients with metastatic cutaneous squamous cell carcinoma (CSCC) or patients with locally advanced CSCC who cannot have surgery or radiation. The approval, the first for cemiplimab, was based on results from phase I and II trials in which patients treated with the drug had an overall response rate of 47%, and 61% had a response that lasted for at least 6 months.
The agency also approved the EGFR inhibitor dacomitinib (Vizimpro; Pfizer) as a first-line treatment for patients with metastatic, EGFR-mutated non–small cell lung cancer. The approval was based on results of the phase III ARCHER 1050 trial, in which patients treated with the drug had a median progression-free survival (PFS) of 14.7 months, compared with 9.2 months in patients who received gefitinib (Iressa; AstraZeneca). The approval is the first for dacomitinib.
Adaptive Biotechnologies announced that the FDA authorized marketing of the clonoSEQ Assay to detect minimal residual disease (MRD) in patients with acute lymphoblastic leukemia or multiple myeloma. The assay uses next-generation sequencing technology to assess disease burden based on the number of cancer cells in a patient’s bone marrow—it can detect MRD at levels under one in a million cells.
The Nobel Prize in Chemistry was awarded to three researchers whose work has improved drugs and biofuels. Francis Arnold, PhD, won half the award for conducting the first directed evolution of enzymes: her technique has produced enzymes used in the more environmentally-conscious production of drugs and biofuels. George Smith, PhD, and Sir Gregory Winter, PhD, shared the other half: the former developed a method of genetically engineering bacteriophages, and the latter applied this method to direct the evolution of new antibodies used in drug development.

Regular aspirin use may reduce the risk of liver and ovarian cancer, according to a pair of studies in JAMA Oncology. In one study, people who took a standard 325 mg dose of aspirin at least twice a week had a 49% reduced risk of developing liver cancer. In another study, women who regularly took a low dose of aspirin (100 mg or less) had a 23% lower risk of ovarian cancer.
AmerisourceBergen will pay $625 million in a civil fraud settlement. The settlement comes after the company was charged with selling syringes of chemotherapeutics prepared in an unsterile environment, billing multiple doctors for the same drug vial, and paying kickbacks to encourage doctors to buy drugs through its prefilled syringe program.
PFS is not indicative of health-related quality of life (HRQoL) in patients with cancer, according to findings in JAMA Internal Medicine. Researchers analyzed 52 articles reporting on 38 randomized clinical trials across 12 types of cancer and did not find a significant association between PFS and global, physical, or emotional HRQoL.
Alpaca antibodies may inhibit epidermal growth factor (EGF), according to a study in Angewandte Chemie. Researchers injected EGF into alpacas and found that the animals produced a family of EGF-inhibiting antibodies, including ones that have a high affinity and strong selectivity for the protein.

September 2018

September 21–27

The FDA approved duvelisib (Copiktra; Verastem), a PI3Kδ/PI3Kɣ inhibitor, to treat patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), as well as patients with relapsed/refractory follicular lymphoma (FL). The approvals were based on results from the phase III DUO trial and the phase II DYNAMO trial: In the former, patients with CLL/SLL treated with the drug had a median progression-free survival (PFS) of 16.4 months, compared with 9.1 months in patients who received ofatumumab (Arzerra; Novartis); in the latter, patients with FL treated with the drug had an overall response rate of 42%.
The agency also approved the tyrosine kinase inhibitor dacomitinib (Vizimpro; Pfizer) as a first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) who have certain EGFR mutations. The approval was based on results from the phase III ARCHER 1050 trial in which patients treated with the drug had a median PFS of 14.7 months and a median duration of response of 14.8 months, compared with 9.2 months and 8.3 months, respectively, in patients who received gefitinib (Iressa; AstraZeneca).
Epizyme announced that the FDA lifted a partial clinical hold on tazemetostat, an EZH2 inhibitor. The hold, initiated after a study participant with advanced chordoma developed a secondary T-cell lymphoblastic lymphoma, was lifted following a comprehensive assessment of the risk of secondary malignancies.
AstraZeneca’s PD-L1 inhibitor durvalumab (Imfinzi) may improve overall survival (OS) in patients with inoperable stage III NSCLC whose cancer has not worsened after chemoradiotherapy, according to results presented at the 2018 World Conference on Lung Cancer (WCLC) in Toronto, Canada, and concurrently published in The New England Journal of Medicine (NEJM). In the phase III PACIFIC trial, patients treated with the drug did not reach median OS, compared with an OS of 28.7 months in patients who received a placebo. The FDA approved durvalumab for this indication earlier this year based on PFS data.

Results also presented at WCLC and simultaneously published in the NEJM indicated that Takeda’s ALK inhibitor brigatinib (Alunbrig) may be an effective first-line treatment for patients with advanced ALK-positive NSCLC. In the phase III ALTA-1L trial, patients treated with the drug had an estimated 12-month PFS rate of 67% and an objective response rate of 71%, compared with 43% and 60%, respectively, in patients who received crizotinib (Xalkori; Pfizer).
Agilent Technologies announced it will acquire ACEA Biosciences for $250 million. ACEA has developed a line of real-time cell analysis instruments that are used in immuno-oncology preclinical drug discovery and development, and basic research.
The Biden Cancer Initiative hosted a Biden Cancer Summit that included a main event in Washington, DC, and 450 other community events around the United States. The summit brought together patients, survivors, caregivers, clinicians, and researchers, as well as 50 companies and organizations. "Our focus is straightforward: to create the cancer research and care system that most people think we already have—and that we all deserve," said former Vice President Joe Biden, co-chair of the Initiative.

September 14–20

A joint U.S. House of Representatives and Senate conference committee approved a $2 billion increase for the NIH for fiscal year 2019 as part of a bipartisan appropriations bill. The legislation, which includes a total of $39.1 billion for the NIH, must now be approved by the full House and Senate before being sent to President Donald Trump for his signature.
Also, the committee nixed an amendment requiring pharmaceutical companies to include drug prices in television ads. The amendment, which was opposed by House members on the committee, passed in the Senate last month.
Bristol-Myers Squibb’s nivolumab (Opdivo) plus ipilimumab (Yervoy; Merck) may benefit women with recurrent epithelial ovarian cancer, according to results presented at the 17th Biennial Meeting of the International Gynecologic Cancer Society in Kyoto, Japan. In the phase II NRG-GY003 trial, 31.4% of women treated with the combination responded within 6 months, compared with 12.2% of women who received nivolumab alone. The combination is approved for certain forms of melanoma, renal cell carcinoma, and colorectal cancer.
Mersana Therapeutics announced that the FDA lifted a partial clinical hold on XMT-1522, an antibody–drug conjugate that targets HER2-expressing tumors. The hold, initiated following a patient death in a phase I trial, was removed after the company agreed to change its protocols to increase patient monitoring and exclude patients with advanced liver failure.

In the United States, spending on cancer drugs increased from $26.8 billion in 2011 to $42.1 billion in 2016, according to a study published in the Journal of Oncology Practice. Spending increased the most for nivolumab, pertuzumab (Perjeta; Genentech), and pembrolizumab (Keytruda; Merck), and decreased the most for oxaliplatin, docetaxel, and gemcitabine; rituximab (Rituxan; Genentech), bevacizumab (Avastin; Genentech), and trastuzumab (Herceptin; Genentech) maintained the highest expenditures.
An artificial intelligence tool may be able to diagnose patients with lung cancer, according to findings published in Nature Medicine. Researchers developed a machine-learning program by training a deep neural network with slide images of cancerous tissues from The Cancer Genome Atlas. Their program distinguished between adenocarcinomas and squamous cell carcinomas with 97% accuracy, and determined the presence of STK11, EGFR, FAT1, SETBP1, KRAS, and TP53 mutations with 73% to 86% accuracy.
In an effort to provide a post-Brexit collaboration model, three cancer charities awarded $39.4 million to cancer research projects in the UK and Europe. Cancer Research UK, Associazione Italiana per la Ricerca sul Cancro in Italy, and Asociación Española Contra el Cáncer in Spain gave 5-year Accelerator Awards to six international collaborations focused on translational research such as devising a blood test for advanced prostate cancer, investigating drug resistance in blood cancers, and developing immunotherapies for liver cancer.

September 7–13

The FDA approved moxetumomab pasudotox-tdfk (Lumoxiti; AstraZeneca) to treat patients with relapsed/refractory hairy cell leukemia who did not respond to at least two prior treatments. The decision was based on findings from a single-arm, open-label trial of 80 patients: 30% achieved a durable complete response, with an overall response rate of 75%. Moxetumomab pasudotox-tdfk is a CD22-directed recombinant immunotoxin.
The FDA also took action against teen use of electronic cigarettes (e-cigarettes), claiming that it has become "an epidemic." The agency gave e-cigarette makers 60 days to prove that they can keep the devices away from teens; if they cannot, device cartridges containing flavors deemed appealing to children may be removed from the market. The FDA also sent more than 1,300 warning letters to retailers caught selling the products to minors, and issued 131 fines.
The American Association for Cancer Research (AACR) released its annual Cancer Progress Report. Available at http://cancerprogressreport.org, it includes the latest information on cancer mortality, diagnosis, prevention, and treatment. The organization also led the sixth annual Rally for Medical Research Hill Day, joining nearly 350 other organizations to advocate for robust, sustained, and predictable annual funding increases for the NIH.
Boehringer Ingelheim announced that it will acquire ViraTherapeutics, which develops oncolytic immunotherapies, for $244 million. ViraTherapeutics' lead candidate, a modified version of the vesicular stomatitis virus, is currently undergoing preclinical testing alone and in combination with other cancer drugs.

A study in Nature analyzed almost 4,000 BRCA1 mutations engineered into the gene in the lab. Researchers developed a CRISPR-based technique called “saturation genome editing” to make thousands of modifications to BRCA1, measuring the effect of each one on human cells. The data will be released through a database to help clinicians interpret BRCA1 variants of unknown significance.
Almost half of all European-registered clinical trials failed to report results, according to findings in The BMJ. Researchers found that only 11% of completed trials funded by noncommercial sponsors, such as universities, hospitals, governments, and charities, and 68% funded by commercial sponsors, such as drug companies, published results on the European Union Clinical Trials Register within 1 year of completion, as required by the European Commission.
The Broad Institute of MIT and Harvard in Cambridge, MA, won a key CRISPR patent battle. The U.S. Court of Appeals for the Federal Circuit in Washington, DC, upheld a previous decision by the U.S. Patent and Trademark Office that the Broad’s 2014 patents on CRISPR/Cas9 for editing plant and animal genomes do not overlap with pending CRISPR patent applications filed by the University of California, Berkeley.

August 31–September 6

A federal court ordered the FDA to move forward on issuing a final rule for graphic health warnings on cigarette packaging and advertising. The ruling from the U.S. District Court for the District of Massachusetts came in a lawsuit filed by the American Academy of Pediatrics, the American Lung Association, and six other groups claiming that the FDA has unreasonably delayed the rule. By the end of this month, the FDA must provide an expedited schedule for releasing the rule.
Blood-testing company Theranos will shut down after criminal charges of fraud were filed against its founder and former CEO, Elizabeth Holmes. Holmes falsely claimed that the company’s technology could use a few drops of blood to test for diseases ranging from diabetes to cancer.
Researchers developed a “homing system” that may help T cells penetrate brain tumors, which is described in Nature. The team reengineered CD6 proteins to trigger the anchoring of T cells to the activated leukocyte cell adhesion molecule, and to increase the sensitivity of T cells to the intercellular adhesion molecule, which resulted in T cells being removed from circulation and entering glioblastoma and medulloblastoma tumors.

Loxo Oncology announced that the FDA granted a breakthrough therapy designation to the selective RET inhibitor Loxo-292 for patients with RET fusion–positive non–small cell lung cancer and RET-mutant medullary thyroid cancer who have not responded to other therapies. The designation is based on results from the ongoing phase I/II LIBRETTO-001 trial.
A company called Driver, which aims to match cancer patients with clinical trials, began operations. The company will charge patients to analyze their tumor samples and medical records, and then use the results to recommend approved treatments and clinical trials—and facilitate referrals via a smartphone app. More than 30 cancer centers in the United States, China, and Singapore have signed up to give clinicians access to a version of the app.
A UK-based guidance urges doctors to avoid medical jargon when writing letters to patients summarizing medical visits and providing test results. The guidance, released by the Academy of Medical Royal Colleges, directs doctors to use short sentences in plain English, cover one topic per paragraph, and avoid acronyms and Latin phrases, among other things.

August 2018

August 24–30

The FDA announced a pilot program to help drug developers use and gain regulatory input on complex innovative trial designs (CID) in their clinical development programs. CIDs include the use of seamless trial designs, modeling and simulations to assess trial operating characteristics, biomarker-enriched populations, Bayesian models, and other novel designs. The agency plans to share CID approaches considered through the pilot program with the broader scientific community.
The FDA issued draft guidance on the use of placebos and blinding in randomized controlled trials for drug development to treat hematologic malignancies and solid tumors. Trials using placebos may be preferred in some cases, such as when surveillance is the standard of care, but their use poses ethical dilemmas in cases where a standard, effective therapy is available. The guidance notes that trial sponsors should provide the rationale for the trial design and makes several recommendations, such as unblinding a patient at the time of disease recurrence or progression.
AbbVie announced that the FDA approved the combination of ibrutinib (Imbruvica) plus rituximab (Rituxan; Genentech) for the treatment of adults with Waldenström macroglobulinemia (WM), a rare and incurable type of non-Hodgkin lymphoma. The drug duo is the first and only chemotherapy-free combination treatment specifically indicated for the disease. Ibrutinib, a Bruton tyrosine kinase inhibitor, was approved as a single-agent therapy for WM in 2015.

Gilead and Kite announced that the European Commission (EC) authorized the marketing of axicabtagene ciloleucel (Yescarta) for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma after receiving two prior therapies. However, a day later, the UK’s National Institute for Health and Care Excellence (NICE) opted not to back the drug, saying that the price is too high. Gilead said that the company will continue to negotiate with NICE on the cost of the chimeric antigen receptor (CAR) T-cell therapy.
Novartis announced that the EC approved its CAR T-cell therapy tisagenlecleucel (Kymriah) for the treatment of patients up to age 25 with certain B-cell acute lymphoblastic leukemias, and for the treatment of adults with relapsed or refractory DLBCL after two or more systemic therapies.
Arizona Senator John McCain died of glioblastoma on August 25. Coincidentally, his friend Massachusetts Senator Edward Kennedy died of the same cancer exactly 9 years earlier, on August 25, 2009.

August 17–23

The FDA approved pembrolizumab (Keytruda; Merck) in combination with pemetrexed and either cisplatin or carboplatin as a first-line treatment for patients with metastatic, nonsquamous non–small cell lung cancer who don’t have EGFR/ALK mutations. The approval was based on results of the phase III KEYNOTE-189 trial, in which patients treated with the combination did not reach median overall survival and had a median progression-free survival of 8.8 months, compared with 11.3 months and 4.9 months, respectively, in patients receiving chemotherapy alone.
The U.S. Senate approved a $2 billion increase to the NIH budget for fiscal year 2019 as part of the 2019 Labor, Health and Human Services, and Education and Related Agencies appropriations bill by a vote of 85-7. The legislation, which includes a total of $39.1 billion for the NIH, earmarks $400 million for the Beau Biden Cancer Moonshot and includes a $90 million increase for the NCI. The U.S. House of Representatives will resume budget discussions following Labor Day.
The U.S. Preventive Services Task Force updated its recommendation for cervical cancer screening to include an option for either primary human papillomavirus (HPV) testing or HPV and Pap cotesting every 5 years in women ages 30 to 65. The previous recommendation provided only an option for cotesting every 5 years in the same group. The change was based on evidence that primary HPV testing is a sufficient screening tool for cervical cancer.
HPV vaccination rates among adolescents increased between 2016 and 2017, according to a report from the Centers for Disease Control and Prevention (CDC). The number of teens ages 13 and 17 who were vaccinated rose by 5%, with almost 66% getting the first dose and 49% completing the vaccination series. However, another CDC report revealed that the number of new cases of HPV-associated cancer climbed from 30,115 in 1999 to 43,471 in 2015; oropharyngeal cancer was the most common form.

Bristol-Myers Squibb’s nivolumab (Opdivo) plus ipilimumab (Yervoy) may be an effective therapy for patients with metastatic melanoma who have untreated brain metastases, according to findings published in The New England Journal of Medicine. In a phase II trial of 94 patients with the disease, 26% had a complete response and 30% had a partial response at a median follow-up of 14 months. Additionally, 2% of patients had stable disease for at least 6 months.
Circulating tumor DNA (ctDNA) levels may predict how well patients with diffuse large B-cell lymphoma respond to treatment, according to a study published in the Journal of Clinical Oncology. Researchers tracked 217 people with the disease, correlating ctDNA levels before, during, and after chemotherapy with response to treatment. They found that patients who had a bigger drop in ctDNA levels during treatment were more likely to live for at least 24 months without disease recurrence.
Researchers developed a tool to predict whether patients with melanoma will respond to immune checkpoint inhibitors. To create the tool, researchers defined gene expression features common to patients with neuroblastoma who had spontaneously undergone tumor regression due to an immune response. In an analysis of 297 patients with melanoma, the tool identified almost all patients who responded to the inhibitors.
The FDA approved two companion diagnostics: the Cobas EGFR Mutation Test v2 (Roche) to identify patients with non–small cell lung cancer who may benefit from gefitinib (Iressa; AstraZeneca), and the Dako PD-L1 IHC 22C3 pharmDx assay (Agilent Technologies) to determine which patients with urothelial carcinoma may respond to pembrolizumab (Keytruda; Merck).

August 10–16

The FDA approved the tyrosine kinase inhibitor lenvatinib (Lenvima; Eisai) as a first-line treatment for patients with inoperable hepatocellular carcinoma. The approval was based on results of the phase III REFLECT trial, in which patients treated with the drug had a median overall survival of 13.6 months, and a median progression-free survival of 7.3 months, compared with 12.3 months and 3.6 months, respectively, in patients who received sorafenib. Lenvatinib is approved for certain forms of thyroid cancer and renal cell carcinoma.
The agency also approved the PD-1 inhibitor nivolumab (Opdivo; Bristol-Myers Squibb) as a monotherapy for patients with small cell lung cancer who have not responded to a platinum-based chemotherapy and at least one other line of therapy. The approval was based on results of the phase I/II CheckMate-032 trial, in which patients treated with the drug had an overall response rate of 12%, and a median duration of response of 17.9 months.
The FDA updated the prescribing information for pembrolizumab (Keytruda; Merck) and atezolizumab (Tecentriq; Genentech) to require the use of an FDA-approved companion diagnostic test to measure PD-L1 levels in tumors of patients with urothelial carcinoma who can’t have cisplatin-based chemotherapy.
A large collection of data on brain cancer became freely available to researchers, the details of which are described in Nature’s Scientific Data. The REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT) dataset includes genomic information from 671 brain tumors—including glioblastomas, astrocytomas, and oligodendrogliomas—collected between 2004 and 2006.

The NCI renewed the comprehensive cancer designation of the Masonic Cancer Center at the University of Minnesota in Minneapolis, and gave the center an “outstanding” rating following its 5-year review. One of 49 NCI-designated comprehensive cancer centers, Masonic leads the Minnesota Cancer Clinical Trials Network.
Many medically underserved women who are eligible for BRCA1/2 testing may not be getting tested, according to a report in JAMA. Researchers analyzed data from 718 low-income women on Medicare who were diagnosed with breast cancer between 2000 and 2014. They found that between 2000 and 2004, none of eligible women received BRCA1/2 testing, while 5% of eligible women received testing between 2005 and 2009 and 15.8% received testing between 2010 and 2014.
State laws designed to increase human papillomavirus (HPV) vaccination among teens don’t influence decisions about becoming sexually active and using condoms, according to findings in Pediatrics. Currently, 23 states and the District of Columbia have passed laws that include providing HPV education in schools, requiring insurers to offer affordable shots, or making the vaccination mandatory. Survey data from 886,981 high school students indicated that similar numbers of teens had sex and used condoms in states with and without legislation.
In The BMJ, researchers proposed removing the term “cancer” from names of certain low-risk conditions. They emphasize that certain cancers—for example, low-risk papillary thyroid cancer—grow slowly or not at all and are unlikely to cause harm, yet the cancer label may motivate some patients to seek unnecessary surgery.

August 3–9

The FDA approved the anti-CCR4 monoclonal antibody mogamulizumab-kpkc (Poteligeo; Kyowa Hakko Kirin) for the treatment of relapsed/refractory mycosis fungoides or Sézary syndrome, two rare forms of non-Hodgkin lymphoma. The approval was based on a phase III trial in which patients treated with the drug had a median progression-free survival of 7.6 months, compared with 3.1 months in patients who received chemotherapy.
The FDA warned that azithromycin may increase the risk of relapse and death in certain patients with blood or lymph node cancers. The agency recommends against prescribing the antibiotic long-term to treat bronchiolitis obliterans syndrome in patients with these cancers who undergo an allogenic stem cell transplant. In the phase III ALLOZITHRO trial, patients treated with the antibiotic had a relapse rate of 32.9% and a 2-year survival rate of 56.6%, compared with 20.8% and 70.1%, respectively, in patients who received a placebo.
Certain germline mutations may increase the risk of triple-negative breast cancer, according to a study in the Journal of the National Cancer Institute. Researchers analyzed genomic data from 10,901 women with the disease and found that BARD1, BRCA1, BRCA2, PALB2, and RAD51D mutations were associated with high risk of triple-negative breast cancer in Caucasian women, and BRIP1, RAD51C, and TP53 alterations were linked to moderate risk. Overall, 12% of participants had a pathogenic variant in one of these genes.

Regeneron Pharmaceuticals and bluebird bio teamed up to develop CAR T-cell therapies, with Regeneron investing $100 million in bluebird. The companies have chosen six initial drug candidates—per the 5-year deal, they will split research costs until a drug reaches clinical trials, at which point Regeneron can opt in 50/50 to continue developing it.
MUC16 mutations may be a useful biomarker for gastric cancer, according to just-published research findings. Researchers analyzed 437 gastric cancer samples from The Cancer Genome Atlas and 256 samples from a cohort of Asian patients and found that MUC16 mutations occurred in 38% of samples from the former and 22% of samples from the latter. The alterations were associated with a significantly greater tumor mutational burden and longer median overall survival (OS).
Broad-based genomic sequencing may not benefit patients with advanced non–small cell lung cancer. In a retrospective study, only 4.5% of patients whose tumors were sequenced received targeted treatment based on the results. Further, sequencing was not associated with an improvement in 12-month mortality or OS compared with patients who had routine testing limited to EGFR and/or ALK mutations.

July 2018

July 27–August 2

Pfizer announced that the European Commission approved PF-05280014 (trazimera), a biosimilar of trastuzumab (Herceptin; Genentech), for patients with HER2-positive breast cancer and metastatic gastric or gastroesophageal junction adenocarcinoma. The FDA declined to approve PF-05280014 in April.
NewLink Genetics cut one third of its staff to cut costs while continuing to develop its IDO inhibitor, indoximod. The company is pursuing the drug as a first-line treatment for acute myeloid leukemia (AML) and diffuse intrinsic pontine glioma, and as a therapy for recurrent pediatric brain cancer. Previously, NewLink announced it would not initiate a phase III trial of the drug in combination with pembrolizumab (Keytruda; Merck) for patients with advanced melanoma, and it “deprioritized” research on pancreatic cancer after the drug did not improve median overall survival (OS) in a phase II trial.
Epizyme will halt a phase II trial assessing the EZH2 inhibitor tazemetostat as a monotherapy and in combination with prednisone in patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL) due to a lack of clinical activity in an interim data analysis. The company will continue two separate trials in DLBCL, as well as in follicular lymphoma and other malignancies. In April, the FDA placed a partial clinical hold on tazemetostat after a pediatric patient taking the drug for advanced chordoma developed a secondary T-cell lymphoma.
Astex/Otsuka’s DNMT inhibitor SCI-110 (guadecitabine) may not be an effective first-line treatment for patients with AML who cannot receive intensive induction chemotherapy. In the phase III ASTRAL-1 trial, the drug did not improve complete response or OS rates compared with standard-of-care chemotherapy. The companies will continue to evaluate the drug in other blood cancers.

Daiichi Sankyo announced that the FDA granted a breakthrough therapy designation to FLT3 inhibitor quizartinib for patients with relapsed or refractory FLT3-mutant AML. The designation is based on results from the phase III QuANTUM-R trial, in which the drug extended OS compared with chemotherapy.
Globally, lung cancer mortality rates among women could rise 43% by 2030, according to a study in Cancer Research. Researchers analyzed mortality data from 52 countries and predicted that the age-standardized mortality rate for women with lung cancer will increase from 11.2 to 16 deaths per 100,000 person years between 2015 and 2030. They also found that death rates are higher in high-income countries than in middle-income countries.
The NCI awarded $33.4 million to the University of Michigan Rogel Cancer Center in Ann Arbor and renewed the center’s designation as a comprehensive cancer center for the next 5 years. The grant, which will support seven research programs in basic science, clinical and translational research, and population sciences, will be spread over 5 years. Rogel is one of 49 NCI-designated comprehensive cancer centers.

July 20–26

Agios Pharmaceuticals announced the approval of ivosidenib (Tibsovo), the first isocitrate dehydrogenase 1 (IDH1) inhibitor OK’d by the FDA, to treat patients with relapsed or refractory acute myeloid leukemia who have IDH1 mutations. The agency concurrently approved the RealTime IDH1 Assay (Abbott Laboratories), a companion diagnostic. The approval was based on results of a phase I trial in which 24.7% of patients achieved complete remission.
The agency also approved filgrastim-aafi (Nivestym; Pfizer), a biosimilar of filgrastim. The drug reduces the risk of infection due to neutropenia in patients with cancer who are undergoing various treatments, including myelosuppressive chemotherapy and bone marrow transplant. Filgrastim-sndz (Zarxio; Sandoz), another filgrastim biosimilar, was the first biosimilar approved by the FDA.
AstraZeneca, Celgene, Merck, and Roche announced they will limit drug price increases for the remainder of 2018. The decisions followed criticism by President Donald Trump about the high cost of drugs. Novartis and Pfizer made similar pledges earlier this month.
Massachusetts launched a probe into Juul Labs, which manufactures electronic cigarettes (e-cigarettes) that look like flash drives. Attorney General Maura Healy sent subpoenas to Juul to obtain information about whether the company is tracking underage e-cigarette use and whether its marketing practices target young people. Healy also sent cease-and-desist letters to two online stores for selling vaping products to minors.

Mersana Therapeutics announced that the FDA ordered a partial clinical hold on XMT-1522, an antibody–drug conjugate (ADC) that targets HER2-expressing tumors. The decision came after a patient died in a phase I trial testing the drug in certain forms of breast, gastric, and lung cancers. The hold does not affect XMT-1536, an ADC in phase I trials for Na2b-expressing cancers.
Massachusetts Governor Charlie Baker signed legislation that designates cancer as a work-related injury for firefighters across the state. The law will cover cancer treatments for firefighters, as well as time missed at work due to illness. Studies have linked smoke inhalation to various types of cancer, and in 2017 the CDC reported that firefighters are 9% more likely to be diagnosed with cancer and are 14% more likely to die from a cancer-related cause than the general population.
The FDA approved a magnetic device system for guiding lymph node biopsies in patients with breast cancer who are having mastectomies. The Magtrace and Sentimag Magnetic Localization System (Endomagnetics) uses magnetic detection during a sentinel lymph node biopsy to identify sentinel lymph nodes that should be surgically removed. The approval was based on results from a trial in which the system detected 94.3% of sentinel lymph nodes, compared with 93.5% detection with the standard gamma probe approach.

July 13–19

Novartis announced that it will not increase drug prices in 2018. The move comes after Pfizer, under pressure from President Donald Trump, agreed to delay price increases on some drugs until the end of the year. “When I looked at the policy environment in the U.S. with our team, we thought the prudent thing to do was to pull back on any further price increases in 2018 and evaluate as the environment evolves,” Vas Narasimhan, MD, Novartis CEO, told Bloomberg Television.
Astellas/Pfizer announced that the FDA expanded the approval of enzalutamide (Xtandi) to include nonmetastatic, castration-resistant prostate cancer. The approval was based on results from the phase III PROSPER trial, in which men treated with the drug plus androgen deprivation therapy (ADT) had a median metastasis-free survival of 36.6 months, compared with 14.7 months in men who received ADT alone. Enzalutamide was previously approved for men with metastatic disease.
The agency also approved the CDK4/6 inhibitor ribociclib (Kisqali; Novartis) in combination with an aromatase inhibitor to treat women with HR-positive/HER2-negative advanced/metastatic breast cancer. In addition, the combination of ribociclib and fulvestrant was greenlighted to treat postmenopausal women with the disease. The approvals were the first granted as part of two pilot programs: Real-Time Oncology Review, which allows the FDA to review information from clinical trials as they progress, and Assessment Aid, a structured template that helps companies submit applications in a format that facilitates the agency’s review.

Roche announced that the FDA granted a breakthrough therapy designation to the PD-L1 inhibitor atezolizumab (Tecentriq) in combination with bevacizumab (Avastin) as a first-line treatment for patients with advanced hepatocellular carcinoma. The designation is based on results from a phase Ib trial in which 15 of 23 patients responded to the combination, which is now being tested in the phase III IMbrave 150 trial.
In the United States, deaths due to liver cancer increased between 1999 and 2016, researchers reported. Overall, there was a 2.1% increase in mortality over the study period, with a consistent 1.3% increase for women, and a 2.6% increase for men until 2010, at which point the increase dropped to 1.3%.
Juul Labs began selling its electronic cigarettes (e-cigarettes) in England and Scotland. The company, which makes e-cigarettes that look like USB drives, holds 68% of the market share in the United States. Juul expanded to Israel in February and is now looking to enter the Asian market.
The NCI renewed the comprehensive cancer center designation of the University of Chicago Medicine Comprehensive Cancer Center in Illinois, and gave the center a “high impact” rating in a review that happens every 5 years. One of 49 NCI-designated comprehensive cancer centers, the center diagnoses and/or treats more than 7,500 patients with cancer every year and participates in more than 350 clinical trials.

July 6–12

Bristol-Myers Squibb announced that the FDA approved nivolumab (Opdivo) plus ipilimumab (Yervoy) for patients ages 12 and older with colorectal cancer who have microsatellite instability–high or mismatch repair–deficient disease and did not respond to fluoropyrimidine, oxaliplatin, and irinotecan. The approval was based on results of the phase II CheckMate-142 trial, in which 119 patients treated with the combination had an overall response rate of 49%, and of those who responded, 83% had a response for least 6 months.
Scientists may be able to predict if individuals are at risk of developing acute myeloid leukemia (AML), according to a study in Nature. Researchers analyzed blood samples from 95 individuals who developed AML and 414 healthy controls and found that those who developed the disease had a greater frequency of mutations in certain genes. The team used this information to create a predictive model that can identify individuals at greater risk.
National and regional governments in Germany will spend almost $98 million to create the LOEWE Centre Frankfurt Cancer Institute following a recommendation by the German Council of Science and Humanities. The institute will be housed on Goethe University’s Niederrad Campus in Frankfurt. "The Frankfurt Cancer Institute...will contribute not only to our scientific understanding of cancer but also to its more targeted treatment," said Birgitta Wolff, president of Goethe University.
The FDA issued a draft guidance about revamping prescription drug labels. With the document, the agency aims to make labels clearer about the conditions and patient populations drugs are intended to treat, and to reduce clutter from unnecessary information. The FDA will release a final guidance after addressing any concerns raised during the current 60-day comment period.

London, UK–based biomedical research charity Wellcome Trust will devote $330 million to funding high-risk projects through the new Wellcome Leap Fund. “We want to take advantage of the surprising, left-field ideas that pose the question ‘what if?’ and support them in a new way that complements our existing funding structures,” said Wellcome director Jeremy Farrar. The fund will run for 5 years starting in 2020.
The proteasome inhibitor ixazomib (Ninlaro; Takeda) may be an effective adjuvant therapy for patients with multiple myeloma: In the phase III TOURMALINE-MM3 trial, patients who received the drug after responding to high-dose chemotherapy and an autologous stem-cell transplant had significantly longer progression free survival (PFS) than patients who received a placebo. Ixazomib is FDA approved in combination with lenalidomide (Revlimid; Celgene) and dexamethasone as a second-line treatment for the disease.
CTI Biopharma Corp announced that its topoisomerase II inhibitor pixantrone (Pixuvri) in combination with rituximab (MabThera; Roche) did not significantly improve PFS in patients with aggressive B-cell non-Hodgkin lymphoma compared with gemcitabine plus rituximab. The results came in the phase III PIX306 trial of 312 patients who had relapsed after chemotherapy and were not eligible for stem-cell transplant. Pixantrone has conditional approval from the European Union as a monotherapy for relapsed/refractory disease.

June 29–July 5

Europe's Committee for Medicinal Products for Human Use recommended approval of two CAR-T cell therapies: tisagenlecleucel (Kymriah; Novartis) for acute lymphoblastic leukemia and diffuse large B-cell lymphoma (DLBCL), and axicabtagene ciloleucel (Yescarta; Gilead/Kite) for DLBCL and primary mediastinal B-cell lymphoma. The agency also recommended approval of daunorubicin/cytarabine (Vyxeos; Jazz Pharmaceuticals) for acute myeloid leukemia and, reversing its previous position, neratinib (Nerlynx; Puma Biotechnology) for adjuvant treatment of HER2-positive breast cancer.
Primary human papillomavirus (HPV) testing may be more effective than Pap testing at detecting precancerous lesions associated with cervical cancer, according to findings published in the Journal of the American Medical Association (JAMA). In the HPV FOCAL trial of 19,009 women, researchers found that HPV testing detected precancerous cervical lesions earlier and with more accuracy than Pap testing over a 4-year period. The U.S. Preventive Services Task Force recommends that women ages 30 to 65 have a Pap test every 3 years or Pap and HPV testing every 5 years, but the group is currently updating its guidelines.
Aptose announced that the FDA lifted a 3-year clinical hold on APTO-253, the company's experimental drug for hematologic cancers that inhibits MYC expression. Aptose will resume a phase Ib study testing the drug in patients with acute myeloid leukemia or with myelodysplastic syndromes. It also plans to assess the drug in patients with B-cell malignancies.
Exelixis's tyrosine kinase inhibitor cabozantinib (Cabometyx) may extend survival in patients with advanced hepatocellular carcinoma who no longer respond to other treatments, according to a study in The New England Journal of Medicine. In the phase III CELESTIAL trial, patients treated with the drug had a median overall survival (OS) of 10.2 months and a median progression-free survival (PFS) of 5.2 months, compared with an OS of 8 months and a PFS of 1.9 months in those who received a placebo. The drug has FDA approval for advanced renal cell carcinoma.

According to a report from the Centers for Disease Control and Prevention, 171,432 cases of pediatric cancer were identified between 2003 and 2014, with an incidence rate of 173.7 cases per 1 million people. Leukemias were most common, with an incidence rate of 45.7, followed by brain tumors (30.9) and lymphomas (26.2). Regional incidence was highest in the Northeast (188) and lowest in the South (168), and state incidence was highest in New Hampshire (205.5), the District of Columbia (194), and New Jersey (192.3).
Survivors of pediatric cancer may be more likely to develop endocrine diseases, according to recent findings published in JAMA Network Open. In a Danish, population-based cohort study, researchers compared 32,548 cancer survivors diagnosed between ages 15 to 39 with 188,728 matched, cancer-free control subjects. They found that the survivors were 73% more likely to develop endocrine disorders, including testicular, ovarian, and pituitary hypofunction and thyroid disease, than healthy controls.
The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology, two of the world's leading organizations for oncology professionals, called upon governments to renew their political commitment to improve cancer services and reduce cancer deaths. "We urgently need governments to work with us and ensure that we have enough oncology professionals, and the necessary resources, to apply our knowledge and save lives," said Alexandru Eniu, MD, PhD, chair of the ESMO Global Policy Committee.

June 2018

June 22–28

Array BioPharma announced that the FDA approved encorafenib (Braftovi) in combination with binimetinib (Mektovi) for patients with inoperable or metastatic melanoma with a BRAF V600E or V600K mutation. The approval was based on results of the phase III COLUMBUS trial, in which patients treated with the combination had a median progression-free survival (PFS) of 14.9 months and a median overall survival (OS) of 33.6 months, compared with 7.3 months and 16.9 months, respectively, in patients who received vemurafenib (Zelboraf; Genentech) alone.
The NIH could receive a $2 billion budget increase in fiscal year 2019, based on a bill introduced by the U.S. Senate’s Labor, Health and Human Services, and Education appropriations subcommittee. The legislation, which would boost the agency’s budget to $39.1 billion, includes money earmarked for Alzheimer’s research, the BRAIN initiative, the All of Us precision medicine study, and the 21st Century Cures Act. The House appropriations subcommittee recently introduced a bill that would increase the NIH budget to $38.3 billion in 2019.
Patients with glioma and MGMT methylated tumors live longer after treatment with temozolomide and radiotherapy than patients with unmethylated tumors, according to a study in JAMA Oncology. In a retrospective analysis of 129 patients, those with MGMT methylated tumors did not reach median OS or median PFS, whereas those with unmethylated tumors had an OS of 3 years and a PFS of 2 years.
Astellas/Medivation’s enzalutamide (Xtandi) may be an effective therapy for certain men with prostate cancer, according to findings in The New England Journal of Medicine. A phase III trial enrolled men with nonmetastatic castration-resistant disease who had rising PSA levels but no visible metastasis on scans. Researchers found those treated with the drug had a median metastasis-free survival of 36.6 months, compared with 14.7 months for those who received a placebo. Enzalutamide was FDA-approved for metastatic castration-resistant prostate cancer in 2012.

Nanobiotix announced that a phase II/III trial of NBTXR3 met its primary and secondary endpoints. NBTXR3 is a radio enhancer: Once activated by radiotherapy, it targets and destroys cancer cells, thus amplifying the effect of the radiation In the trial, 16.1% of patients with soft-tissue sarcoma treated with the drug plus radiotherapy achieved a pathologic complete response, compared with 7.9% of patients who received radiotherapy alone.
The NCI awarded $31.9 million to the Case Comprehensive Cancer Center in Cleveland, OH, and rated it as exceptional after completing a review of Case’s programs, which happens every 5 years. One of 49 NCI-designated comprehensive cancer centers, Case treats almost 16,000 new patients with cancer each year. The award includes a $27.9 million research grant to be spread over 5 years, and $4 million to support training and career-development programs.
SpaceX launched its Dragon cargo ship, which will carry Angiex’s anti-TM4SF1 antibody–drug conjugate to the International Space Station. Scientists will test the drug on endothelial cells (EC) cultured in microgravity, which are hypothesized to have similar qualities as in vivo resting endothelium. Scientists hope the research will show that ECs grown in microgravity can be used as an in vitro system to investigate cancer drug toxicity.

June 15–21

Tabelecleucel (Tab-cel; Atara), an off-the-shelf T-cell therapy, may improve survival for patients with Epstein–Barr virus–associated post-transplant lymphoproliferative disorder, according to findings reported at the 23rd Congress of the European Hematology Association in Stockholm, Sweden. In a phase II trial, patients who developed the disorder following hematopoietic cell transplant and subsequently received the therapy had an overall response rate (ORR) of 69% and overall survival (OS) rates of 68% at 1 year and 55% at 3 years. In another phase II trial, patients who were treated following solid organ transplant had an ORR of 50% and OS rates of 64% at 1 year and 43% at 3 years.
The FDA restricted the use of pembrolizumab (Keytruda; Merck) and atezolizumab (Tecentriq; Genentech) in patients with advanced urothelial cancer: Now, patients who are not eligible for cisplatin-containing therapy can be treated with the drugs only if they have PD-L1 expression above 10% or 5%, respectively. Patients not eligible for any platinum-containing therapy can still receive the checkpoint inhibitors, regardless of PD-L1 expression.
The FDA withdrew a draft guidance on the development of biosimilars issued in September 2017. The guidance was designed to help companies evaluate proposed biosimilars in comparison to existing products. "One of the central aspects of biosimilar development and approval is the analytical studies performed to demonstrate that a biosimilar is highly similar to the reference product," said FDA Director Scott Gottlieb, MD. "We're taking a fresh look at our draft recommendations for evaluating analytical studies in order to ensure our guidance takes into consideration the most current and relevant science."

Recent-onset type 2 diabetes may be an early sign of pancreatic cancer, according to a study in the Journal of the National Cancer Institute. In a prospective study of 48,995 African Americans and Latinos, researchers identified 15,833 who developed diabetes and 408 who developed pancreatic cancer. In total, 52.3% of patients with pancreatic cancer had recent-onset diabetes, meaning within the 36 months before their cancer diagnosis. Overall, diabetes was associated with an approximately twofold greater risk of pancreatic cancer; the increase was even more pronounced in patients with recent-onset diabetes.
TAS-102, a combination of trifluridine and tipiracil (Lonsurf; Taiho Pharmaceutical) may improve survival in patients with metastatic or advanced gastric cancer who haven't responded to other therapies, according to findings reported at the 2018 World Congress on Gastrointestinal Cancer in Barcelona, Spain. In the phase III TAGS trial, patients treated with the drug had an OS of 5.7 months, compared with 3.6 months in patients who received a placebo. TAS-102 has FDA approval for metastatic colorectal cancer in patients who have already received other therapies.
The Centers for Disease Control and Prevention reported that in 2017, 13.9% of U.S. adults were cigarette smokers—the lowest level ever recorded. In 2009, 20.2% of U.S adults smoked cigarettes.

June 8–14

During the past week the FDA approved a host of drugs and approved expanded use of a companion diagnostic. Among the announcements:
- Merck’s PD-1 checkpoint inhibitor pembrolizumab (Keytruda) was greenlighted for the treatment of advanced cervical cancer in women whose disease has progressed on or after chemotherapy and whose tumors express PD-L1. The approval was based on findings of a study in which 77 patients with PD-L1 levels of at least 1% had an overall response rate (ORR) of 14.3%; of those women, nearly all responded to the drug for at least 6 months.
- In conjunction with that pembrolizumab approval, the agency OK’d the expanded use of Agilent’s PD-L1 IHC 223C pharmDx Kit to determine PD-L1 status.
- Pembrolizumab was also approved for the treatment of primary mediastinal large B-cell lymphoma in adults and children, as well as those who have relapsed following at least two other treatments. The decision was based on a phase III trial in which patients treated with the immunotherapeutic had an ORR of 45%.
- Genentech’s bevacizumab (Avastin) plus chemotherapy, followed by bevacizumab monotherapy, was approved for women with advanced ovarian cancer after surgery. In a phase III trial, patients who received that regimen had a median progression-free survival (PFS) of 18.2 months and a median overall survival (OS) of 43.8 months, compared with a PFS of 12.8 months and an OS of 40.6 months in patients who received the combination followed by a placebo.

The agency also expanded the indication for venetoclax (Venclexta; AbbVie and Genentech). It can now be used with rituximab for second-line treatment of patients with chronic lymphocytic leukemia or small lymphocytic lymphoma with or without a 17p deletion. Patients who received this combination regimen as part of a phase III trial had an ORR of 92% and did not reach median PFS, compared with an ORR of 72% and a PFS of 18.1 months in patients who received bendamustine plus rituximab.
The U.S. House of Representatives’ Subcommittee on Labor, Health and Human Services, and Education marked up its appropriations bill for the 2019 fiscal year. The bill proposes $38.3 billion in funding for the NIH, an increase of $1.25 billion. In addition, it proposes a total of $6.136 billion for the NCI, which includes $400 million authorized for the Beau Biden Cancer Moonshot. The bill now goes to the full House Appropriations Committee for consideration; the U.S. Senate has yet to mark up its spending bill.
Gene editing with CRISPR/Cas9 may increase cancer risk, according to two studies in Nature Medicine. The studies, which focused on retinal cells and pluripotent stem cells, found that CRISPR/Cas9 is most effective in human cells that lack functioning p53, a protein that responds to DNA damage by repairing it or instructing cells to self-destruct . However, cells with p53 mutations, although more likely to survive CRISPR/Cas9 editing, are also more likely to cause cancer.
In a Nature Genetics study, researchers reported the identification of 63 new prostate cancer susceptibility loci. The team then used the loci, along with loci from previous studies, to develop a new polygenic risk score. They determined that men who score in the top 1% are 5.7 times more likely to develop prostate cancer than the general population.

June 1–7

The NCI will provide $10 million in additional funding to the National Clinical Trials Network, Director Ned Sharpless, MD, announced at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL. "The majority of this funding will be used to augment per-patient reimbursement rates at 180 sites that treat adult or pediatric cancers,” Sharpless said. The goal is to offset the rising costs of clinical trials and expand trials to include more patients.
Also at the ASCO Annual Meeting, FDA Director Scott Gottlieb, MD, outlined the agency's new policies and initiatives to advance cancer treatment and prevention. He touched on various topics, including tightening regulations on conventional and electronic cigarettes, improving efficiency of the drug development and review process, and increasing representation and enrollment in clinical trials. "We're challenging ourselves at the FDA to make sure that we have the best approach to evaluating new products. And we're doing so in ways that are modern and efficient, so that we're making the best use of our own resources, we're facilitating innovation, and we're fulfilling the needs of patients,” he said.
Many women with early-stage breast cancer may not need chemotherapy after surgery, researchers reported at the ASCO meeting and in The New England Journal of Medicine. In the phase III TAILORx trial, women with hormone receptor–positive, HER2-negative, axillary node–negative breast cancer who received hormone therapy alone had similar disease-free survival and overall survival (OS) as women who received hormone therapy plus chemotherapy. The findings suggest chemotherapy is unnecessary in women older than 50 who score 25 or below on the Oncotype DX Breast Recurrence Score test, and in women 50 and younger who score 15 or below.
In a joint statement, NCI-designated cancer centers called for increased human papillomavirus (HPV) vaccination and evidence-based screening, with the goal of eliminating cancers caused by the virus, such as cervical and head and neck cancers. Currently, the Centers for Disease Control and Prevention (CDC) recommends all children age 11 or 12 receive the two-part HPV vaccine series, yet only 49.5% of girls and 37.5% of boys between ages 13 and 17 completed the series in 2016, according to the CDC.

The FDA approved pegfilgrastim-jmdb (Fulphila; Mylan), the first biosimilar of pegfilgrastim (Neulasta; Amgen). The drug is designed to reduce the risk of infection in patients with nonmyeloid cancer who are receiving chemotherapy and have febrile neutropenia. The approval came after the agency reviewed the structural and functional characterization of the drug, as well as findings from human and animal studies and data on clinical safety and effectiveness.
Black men with advanced prostate cancer may be more responsive to antiandrogen drugs and steroids, according to data presented at the ASCO meeting. Researchers treated 50 black men and 50 white men with abiraterone and prednisone. They found that PSA levels dropped more quickly in black men and did not increase for a median of 16.6 months, compared with 11.5 months for white patients. The median progression-free survival was 16.8 months in both groups.
Pfizer's dacomitinib may improve survivalin patients with advanced or metastatic non–small cell lung cancer with EGFR-activating mutations, according to findings presented at the ASCO meeting and published concurrently in the Journal of Clinical Oncology. In the phase III ARCHER 1050 trial, patients treated with the drug had a median OS of 34.1 months, compared with 26.8 months in patients who received gefitinib (Iressa; AstraZeneca). Dacomitinib, a pan-HER inhibitor, has been granted priority review by the FDA.

May 2018

May 25–31

Adults age 45 and older should be screened for colorectal cancer, according to an updated guideline from the American Cancer Society (ACS). The recommendation, which applies to people of average risk, is based in part on data suggesting that disease rates are increasing in young and middle-aged populations. Until now, the ACS has recommended screening for adults age 50 and older.
The FDA granted priority review to gilteritinib (Astellas) for the treatment of adult patients with FLT3 mutation-positive relapsed or refractory acute myeloid leukemia (AML). The drug is currently being compared with chemotherapy in the ongoing phase III ADMIRAL trial. It received an orphan drug designation from the FDA for AML in 2017.
The agency also granted priority review to larotrectinib (LOXO-101; Loxo Oncology) to treat pediatric and adult patients with TRK fusion-positive solid tumors. In previously published data, 55 patients who received the drug had an overall response rate of 75%. The drug has already received breakthrough therapy, rare pediatric disease, and orphan drug designations from the FDA.
Myriad Genetics bought Counsyl for $375 million. Myriad specializes in genetic screening tests for hereditary cancers—its 28-gene panel, Myriad myRisk, provides a risk assessment for breast, colorectal, and pancreatic cancers, among others. In the deal, Myriad will gain access to Counsyl's leading test, Foresight, which screens for more than 175 conditions, along with its prenatal screening test, Prelude, and its hereditary cancer screening panel, Reliant.

Genmab and Janssen will halt two trials testing daratumumab in combination with anti–PD-L1 therapies. One is the phase Ib/II CALLISTO/LUC2001, in which the combination of daratumumab and atezolizumab did not offer a survival benefit over atezolizumab monotherapy in patients with advanced or metastatic non-small cell lung cancer. Based on these findings, the companies will also discontinue the phase I MMY2036 trial of daratumumab plus the anti–PD-1 antibody JNJ-63723283 in patients with multiple myeloma.
St. Jude Children's Research Hospital is spending more than $100 million to launch St. Jude Global. The goal of the initiative is to influence the care of 30% of children with cancer worldwide over the next decade. It will focus on educating the clinical workforce, strengthening health systems and patient-centered initiatives, and supporting research on pediatric oncology and hematology.

May 18–24

Congress passed "right-to-try" legislation that allows terminally ill patients to seek experimental treatments directly from pharmaceutical companies. The bill, which passed by a vote of 250-169 in the U.S. House of Representatives, was approved by the Senate last year. Previously, patients could apply to the FDA for access via a process called expanded access or compassionate use, which approved 99.5% of requests between 2009 and 2014.
A new screening test for prostate cancer could reduce the number of unnecessary biopsies, according to results presented at the American Urological Association 2018 Annual Meeting. The IsoPSA assay (Cleveland Diagnostics) checks for structural changes in PSA that result directly from prostate cancer; PSA itself is not cancer specific. In a validation study that compared IsoPSA with traditional PSA testing, the former reduced biopsies by 47%.
The FDA released an alert that patients with advanced urothelial cancer and low PD-L1 expression may have decreased survival when treated with pembrolizumab (Keytruda; Merck) or atezolizumab (Tecentriq; Genentech) monotherapy compared with chemotherapy alone. Those findings stem from the phase III KEYNOTE-361 and IMVIGOR-130 trials. In both, the monotherapy arms have stopped enrolling patients with low PD-L1 expression, but are still enrolling patients with high PD-L1 expression; trial arms that include patients receiving a combination of one of the checkpoint inhibitors and chemotherapy are also continuing to accrue patients.
Lung cancer rates are higher among women than men in the United States, according to a recent study in The New England Journal of Medicine (NEJM). Researchers examined data on lung cancer in people ages 30 to 54 and found that the disease was more common among white and Hispanic women than men in almost every age group, a reversal from previous studies. Researchers say that the shifting pattern in incidence could stem from differences in the types of lung cancer affecting men and women and the subsequent reduction of risk after smoking cessation, or differences in susceptibility to the health hazards of smoking.

Also in the NEJM, financial incentives increased the effectiveness of smoking cessation. A study assigned 6,000 participants from 54 U.S.-based companies to usual care information on the benefits of quitting and motivational text messages or usual care plus one of four interventions. They found quitting rates through 6 months were 0.1% for those receiving usual care, compared with 0.5% for those given free nicotine-replacement therapies/cessation medications, plus e-cigarettes if those failed; 1% for those given free e-cigarettes; 2% for those given free cessation aids plus a $600 reward for sustained quitting; and 2.9% for those given free aids plus $600 that had to be returned if certain quitting milestones weren't met.
The Norris Comprehensive Cancer Center and the Keck School of Medicine in Los Angeles, CA, were awarded $43.7 million, to be spread over 10 years, to support the Los Angeles County Cancer Surveillance Program. The registry tracks all cancer cases in the county, more than 44,000 each year, and thus far has collected more than 1.7 million records. The funding will come from NCI's Surveillance, Epidemiology, and End Results Program, which uses 19 registries to gather information on cancer incidence and survival rates nationwide.

May 11–17

The FDA published a list of pharmaceutical companies that have potentially been withholding drug samples from generic manufacturers, along with the names of the specific therapies. The list includes Novartis’s Afinitor (everolimus) and Tasigna (nilotinib) and Celgene’s Pomalyst (pomalidomide) and Revlimid (lenalidomide), among others. "We hope that this increased transparency will help reduce unnecessary hurdles to generic drug development and approval," said FDA Commissioner Scott Gottlieb, MD.
In the United States, only 1.9% of more than 7 million current and former heavy smokers were screened for lung cancer in 2016, according to findings presented during a media preview for the 2018 American Society of Clinical Oncology Annual Meeting. Researchers analyzed data from the 2016 American College of Radiology’s Lung Cancer Screening Registry, which tracked screening at 1,796 sites throughout the country. Screening rates were highest in the Northeast (3.5%) and lowest in the West (1%).
Exelixis announced that atezolizumab (Tecentriq) plus cobimetinib (Cotellic) did not improve overall survival (OS) in patients with advanced colorectal cancer. The negative results came in the phase III IMblaze370 trial, where the combination failed to prolong OS compared with regorafenib (Stivarga; Bayer), the standard treatment. Atezolizumab has FDA approval for certain bladder and lung cancers, and cobimetinib is approved for advanced melanoma.
Eleven new institutions joined the American Association for Cancer Research’s Project Genomics Evidence Neoplasia Information Exchange (GENIE), an international effort to aggregate and make available next-generation sequencing data from patients’ tumors. Thus far, GENIE has publicly released over 39,000 deidentified genomic records, and it is expected to release data from the new institutions in January 2019.

Men and women may have different responses to immunotherapies, according to a study published in The Lancet Oncology. Researchers analyzed 20 published trials involving 11,351 patients with advanced cancers who were treated with immune checkpoint inhibitors. They found that although the drugs improved OS in both men and women, the efficacy of the drugs, on average, was significantly better in men.
Cellectar Biosciences’ drug CLR 131 received orphan drug designation from the FDA for the treatment of patients with rhabdomyosarcoma, a rare pediatric cancer. The drug is a radioiodinated phospholipid drug conjugate that uses phospholipid ether (PLE) and PLE analogues to selectively deliver radiation to tumor cells. CLR 131 previously received orphan drug and rare pediatric disease designations for neuroblastoma.
More U.S. adults are trying electronic cigarettes (e-cigarettes), but fewer are becoming regular users of the devices, according to a report in JAMA. Researchers analyzed data from 101,175 adults gathered by the National Health Interview Survey and found that the percentage of adults who tried an e-cigarette increased from 12.6% in 2014 to 15.3% in 2016, but the percentage of current regular users decreased from 3.7% to 3.2% over the same period.

May 4–10

The human papillomavirus vaccine protects adolescent girls and women against precancerous cervical lesions, according to an analysis of existing research. Investigators examined 26 studies involving 73,428 adolescent girls and women. They concluded, with a high level of certainty, that the vaccine protects against cervical precancer in those who received it between ages 15 and 26, and that it does not increase the risks of serious adverse events, miscarriage, or pregnancy termination.
Novartis announced that the FDA approved the combination of dabrafenib (Tafinlar) and trametinib (Mekinist) to treat patients with advanced BRAF V600E–positive anaplastic thyroid cancer. The approval was based on results of an open-label trial: Among 23 patients treated with the drug, 57% achieved a partial response and 4% had a complete response; overall, 64% of responders had no significant tumor growth for at least 6 months. The combination previously received FDA approval for adjuvant treatment of BRAF V600–mutant melanoma.
Janssen said that the FDA approved daratumumab (Darzalex) in combination with bortezomib, melphalan, and prednisone (VMP) to treat patients with newly diagnosed multiple myeloma who aren’t eligible for autologous stem cell transplant. The approval was based on the phase III ALCYONE trial, in which patients treated with the combination had an objective response rate of 90% and an 18-month progression-free survival rate of 71.6%, compared with 73.9% and 50.2%, respectively, in patients who received VMP alone.

Japan-based Takeda Pharmaceutical will acquire Ireland-based Shire for $62 billion. Shire is known for developing drugs for rare diseases and conditions, such as hemophilia and hereditary angioedema, as well as drugs for attention deficit hyperactivity disorder and ulcerative colitis, among others. Last month, Shire sold its cancer drug portfolio to French pharmaceutical company Servier for $2.4 billion.
Eli Lilly will buy ARMO Biosciences for $1.6 billion. ARMO Biosciences specializes in immuno-oncology drugs. Its leading candidate is pegilodecakin, a PEGylated IL10 under study in a phase III trial in pancreatic cancer, as well as earlier-stage trials in other solid tumor types, including melanoma and lung and renal cancers. The company also has other candidates in preclinical development, including the anti–PD-1 monoclonal antibody AM0001 and the anti-LAG3 checkpoint inhibitor AM0003.
Many oncologists recommend medical marijuana without feeling sufficiently informed about its utility, according to a recent study in the Journal of Clinical Oncology. Researchers surveyed 237 medical oncologists throughout the United States and found that although 80% discussed medical marijuana with patients and 46% recommended it, only 30% felt equipped to make a clinical recommendation about the drug.

April 2018

April 27–May 3

The FDA approved dabrafenib (Tafinlar; Novartis) plus trametinib (Mekinist; GlaxoSmithKline) as an adjuvant treatment for BRAF-mutant stage III melanoma following surgery. The approval was based on the results of the phase III COMBI-AD trial, in which patients treated with the combination had a 3-year relapse-free survival (RFS) rate of 58%, compared with an RFS rate of 39% in those who received a placebo. The combination was previously approved for BRAF-mutant melanoma and non–small cell lung cancer.
The agency also approved tisagenlecleucel (Kymriah; Novartis) to treat adults with relapsed/refractory large B-cell lymphoma. The approval was based on results of the phase II JULIET trial, in which patients treated with the CAR T-cell therapy had an overall response rate of 50%. The therapy received FDA approval in 2017 for the treatment of patients up to age 25 with relapsed/refractory acute lymphoblastic leukemia.
In addition, the FDA designated cancer vaccine BN-Brachyury (Bavarian Nordic) as an Orphan Drug for the treatment of chordoma, a rare type of bone cancer. A phase I trial to evaluate the safety and tolerability of the vaccine is enrolling patients with locally advanced, malignant solid tumors, and a phase II trial in metastatic chordoma is scheduled to begin later this year.

The agency declined to approve Sandoz’s GP2013, a biosimilar of rituximab (MabThera/Rituxan; Roche/Genentech). The CD20 inhibitor, known as Rixathon in Europe, was approved by the European Commission (EC) in June 2017 for certain forms of non-Hodgkin lymphoma, chronic lymphocytic leukemia, and various immune diseases. MabThera/Rituxan has FDA and EC approval for the same indications.
Women with BRCA-mutant advanced triple-negative breast cancer are twice as likely to respond to carboplatin than docetaxel, according to findings published in Nature Medicine. In the phase III TNT trial, women with BRCA gene faults treated with carboplatin had an objective response rate (ORR) of 68%, compared with 33% in those treated with docetaxel. This difference was not present when researchers analyzed ORR across the entire trial population.
Scientists established the complete pathway that produces the chemotherapeutic vinblastine in the Madagascar periwinkle. Two steps on the pathway, which consists of 31 enzyme reactions, were unknown until researchers determined that the enzymes tabersonine synthase and catharanthine synthase are needed to produce the alkaloids tabersonine and catharanthine. Vinblastine is used to treat various cancers, including Hodgkin lymphoma and certain brain and lung cancers.

April 20–26

The FDA declined to approve PF-05280014, Pfizer’s biosimilar of trastuzumab (Herceptin; Roche), requesting additional technical details about the drug. The FDA approved trastuzumab-dkst (Ogivri), Mylan’s biosimilar of the drug, in December 2017. Trastuzumab and trastuzumab-dkst are approved for certain forms of breast and gastric cancers.
AstraZeneca announced that combining tremelimumab with durvalumab (Imfinzi) does not improve survival in patients with advanced non–small cell lung cancer (NSCLC) and low PD-L1 expression. The results came in the phase III ARCTIC trial, where patients in the low PD-L1 group treated with the combination did not have longer overall or progression-free survival compared with patients who received standard chemotherapy. Durvalumab received FDA approval in February to treat patients with advanced NSCLC following chemoradiation.
The FDA is enforcing laws prohibiting retailers from selling electronic cigarettes (e-cigarettes), particularly Juuls, to minors. During an ongoing undercover, nationwide blitz of brick-and-mortar and online stores, the agency has uncovered dozens of violations and issued 40 warning letters related to Juul e-cigarettes. The FDA has also contacted Juul Labs to request information on marketing, health effects, and design features of the devices.
A subsidiary of Johnson & Johnson, Cerenovus is no longer making chemotherapy pumps for patients with colorectal liver metastases, citing low demand and manufacturing constraints. The devices, called Codman pumps, are implanted into the abdomen and deliver high doses of chemotherapy directly to the liver. In a retrospective study, patients who received the pumps had a median overall survival (OS) of 67 months, compared with an OS of 44 months in patients who did not.

A subsidiary of Johnson & Johnson, Cerenovus is no longer making chemotherapy pumps for patients with colorectal liver metastases, citing low demand and manufacturing constraints. The devices, called Codman pumps, are implanted into the abdomen and deliver high doses of chemotherapy directly to the liver. In a retrospective study, patients who received the pumps had a median overall survival (OS) of 67 months, compared with an OS of 44 months in patients who did not.
The FDA ordered a partial clinical hold on tazemetostat (Epizyme), an EZH2 inhibitor being tested in phase I and II trials as a treatment for various solid tumors and blood cancers. The hold came after a patient with advanced chordoma receiving the drug developed a secondary T-cell lymphoma. During the hold, trials will not enroll additional patients, but existing patients without disease progression can continue treatment.
Radiotherapy given in higher doses over a shorter time period is safe and effective for patients with prostate cancer, according to research presented at ESTRO 37 in Barcelona, Spain. In a trial of 1,200 patients, 83.7% of those who received ultrahypofractionated radiotherapy—seven higher doses of radiation over 2.5 weeks—were cancer-free after 5 years, compared with 83.8% of those who received standard radiotherapy—39 lower doses of radiation over 8 weeks.

April 13–19
This Week: Special Content from the American Association for Cancer Research’s (AACR) Annual Meeting 2018 and other news

Speaking at the AACR meeting’s Opening Plenary, Padmanee Sharma, MD, PhD, offered a brief history of the development of checkpoint inhibitors and efforts to discover and study additional targets, such as CD40 and ICOS for costimulation of T cells, and CD47 and VISTA, which are predominantly expressed on macrophages. "Immune checkpoint therapies are certainly joining the ranks of surgery, radiation, and chemotherapy as a pillar of cancer research," she said. "We need to understand that multiple immune checkpoints exist and are dynamic in their expression."
George Coukos, MD, PhD, of the Ludwig Center for Cancer Research, University of Lausanne, Switzerland, presented data from a pilot clinical trial that tested personalized neoantigen vaccines in 25 patients with recurrent ovarian cancer. Data showed that the therapy was feasible, well tolerated, and safe, both alone and in combination with one or the two other treatments. Patients in whom the vaccine could effectively mobilize neoepitope-specific T-cell responses had significantly prolonged survival.
"I would say that it's like Coke and Pepsi—they’re two similar flavors from two different companies in two different packages," said Antoni Ribas, MD, PhD, of the University of California, Los Angeles, in comparing the PD-1 inhibitors nivolumab (Opdivo; Bristol-Myers Squibb) and pembrolizumab (Keytruda; Merck).
The Lustgarten Foundation and Stand Up To Cancer (SU2C) announced that they are partnering to accelerate research to increase survival of patients with pancreatic cancer. The two groups will fund the Pancreatic Cancer Collective with an initial commitment of $25 million. The money will be used to launch new collaborative efforts, leverage artificial intelligence, improve and develop new diagnostics and treatments for pancreatic cancer, and support the next generation of pancreatic cancer researchers. The AACR is SU2C’s scientific partner.
The AACR and the UBS Oncology Impact Fund (OIF) managed by MPM Capital announced a gift of $1.25 million to fund the joint AACR–MPM Transformative Cancer Research Grants Program to support innovative research that will accelerate breakthroughs in the treatment of cancer. The OIF is a first-of-its-kind social-impact fund dedicated to investing in oncology therapeutics across a spectrum of companies, from early-stage start-ups to public companies. The AACR and MPM are now establishing an expert scientific advisory board whose members will be tasked with selecting grant recipients.
Children with non-chromosomal birth defects are 2.5 times more likely to develop childhood cancers, according to findings presented by Jeremy Schraw, PhD, of Baylor College of Medicine in Houston, TX. Reviewing data on 10.1 million births, Schraw and his team found even stronger associations between certain birth defects and specific cancers—for example, children with spina bifida without anencephaly were at a 74.9-fold higher risk of developing non-rhabdomyosarcoma soft-tissue sarcoma. "We need to better understand the ages at which those children are at risk, we need to validate the findings, and we need to understand the mechanism of that association better before we start making decisions about screening and treatment," he said.

Updated MOSCATO-01 trial results indicate tailoring treatment to the genetic makeup of a patient’s tumor may not improve overall survival (OS). Researchers reported that patients who were matched to targeted therapies based on “actionable” genetic mutations did not have significantly better OS than those who were not. Previous findings from the MOSCATO-1 trial indicated that 33% of patients matched to therapies based on genetic alterations experienced an extended progression-free survival of 30%.
Nivolumab offers a long-term survival benefit to patients with recurrent or metastatic squamous cell carcinoma of the head and neck, according to results of the phase III CheckMate 141 clinical trial presented at the meeting by Robert Ferris, MD, PhD, of the University of Pittsburgh, PA. After 2 years of follow-up, patients who received nivolumab had an OS rate of 16.9%, compared with 6% in patients treated with the investigator’s choice of drug. In patients with PD-L1 tumor expression above and below 1%, the risk of death was reduced by 45% and 27%, respectively. The findings confirm results reported after 1 year of follow-up.
Daniel J. Lenihan, MD, of the Washington University School of Medicine in St. Louis, MO, emphasized the need to consider cardiac issues beyond heart failure in patients receiving cancer treatment. "If you're looking for problems just related to heart failure, you're missing half the boat," he explained, noting that, in the PROTECT study, heart failure represented 50% of the adverse cardiac events experienced by patients with multiple myeloma receiving the proteasome inhibitor carfilzomib (Kyprolis; Onyx). "I really think our new definition of cardiotoxicities must include a lot more," he said, including metabolic issues and structural problems.
"There’s a tremendous effort to enroll minorities in clinical trials with the idea that the drugs work differently in minorities," said Otis Brawley, MD, chief medical and scientific officer and executive vice president of the American Cancer Society, who spoke about disparities in cancer treatment and mortality. "What’s frustrating to me is the data show minorities … aren’t [subsequently] getting the drugs."
Leaders of the AACR and Cancer Research UK announced the launch of an international alliance to speed progress against cancer. The alliance will build trans-Atlantic collaborations by establishing training and exchange programs, catalyzing scientific innovation by convening meetings and workshops, and uniting the cancer community to influence global research policy. The partnership will also foster links between laboratories and clinics in the United States and the UK.
In other news, the FDA approved osimertinib (Tagrisso) for first-line treatment of patients with metastatic non–small cell lung cancer (NSCLC) whose tumors have EGFR mutations, AstraZeneca announced. The approval is based on results of the phase III FLAURA trial. The drug was previously approved for use in patients with EGFR-mutant NSCLC whose disease progressed on or after taking another EGFR therapy and who have developed the secondary T790M mutation. The FDA expanded the use of Roche’s Cobas EGFR Mutation Test v2 to detect the mutations.

April 6–12

The FDA finalized two guidances for the development of next-generation sequencing tests. The first guidance outlines how developers can use clinical evidence from FDA-recognized public databases like ClinGen to support the clinical validation of their tests. The second guidance provides recommendations for designing, developing, and validating tests used to diagnose genetic diseases. "As disease-detection technologies rapidly evolve, so too must the FDA's approach to reviewing these new innovations," said FDA Commissioner Scott Gottlieb, MD.
Merck’s pembrolizumab (Keytruda) improved overall survival (OS) as a first-line monotherapy in patients with locally advanced or metastatic non–small cell lung cancer. Interim results from the KEYNOTE-042 trial showed that patients treated with the PD-1 inhibitor had significantly longer OS than patients who received platinum-based chemotherapy. Pembrolizumab has FDA approval to treat certain forms of skin, lung, urothelial, gastric, and head and neck cancers.
The FDA approved rucaparib (Rubraca; Clovis Oncology) as a maintenance therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are experiencing a complete or partial response to platinum-based chemotherapy. The approval was based on results from the phase III ARIEL3 trial, in which the drug significantly extended progression-free survival. The FDA approved rucaparib for the treatment of advanced ovarian cancer in December 2016.

Personalized immunotherapy treatment may improve survival in patients with advanced, recurrent ovarian cancer, according to a pilot study in Science Translational Medicine. Researchers created personalized vaccines for 25 patients consisting of their own dendritic cells that had been exposed to tumor material. Patients who received the vaccine in combination with either bevacizumab or bevacizumab plus cyclophosphamide had a higher average 2-year survival rate than patients from a previous study who received the drugs without the vaccine.
Pfizer announced it will halt a trial evaluating axitinib (Inlyta) as adjuvant therapy for patients at high risk of recurrent renal cell carcinoma after nephrectomy. The decision was based on results of the phase III ATLAS trial, in which the drug did no better than a placebo at prolonging survival. The FDA approved axitinib to treat advanced renal cell carcinoma in 2012.
Higher cigarette prices would cause millions to stop smoking, according to findings published in the BMJ. Researchers conducted an analysis of 500 million male smokers in 13 countries and found that a 50% increase in the cost of cigarettes would result in 67 million men quitting the habit, and 449 million years of life gained. Men in the poorest 20% of the population would gain 6.7 times more life-years than men in the top 20%, and in the seven countries without universal health care, about 15.5 million men would avoid catastrophic health expenditures.

March 30–April 5

Cancer researchers published The Pan-Cancer Atlas, a database containing genomic and molecular data on 33 types of cancer from more than 10,000 patients. So far, 27 papers have been published in Cell, Cancer Cell, Cell Reports, and Immunity based on the results. The atlas is a product of The Cancer Genome Atlas Network, a collaboration between the NCI and the National Human Genome Research Institute.
Larotrectinib (LOXO-101; Loxo Oncology) is safe and effective in pediatric patients with TRK fusion-positive cancers, according to a study published in The Lancet Oncology. In the phase I/II SCOUT trial, 14 of 15 patients with solid tumors harboring TRK fusions treated with the drug had an objective response. In a study published earlier this year in The New England Journal of Medicine, adult and pediatric patients with TRK fusion–positive cancers treated with larotrectinib had an objective response rate of 75%.
The American Society of Clinical Oncology published a new clinical practice guideline for treating patients with metastatic non-castrate prostate cancer. The guideline recommends treating these patients with androgen-deprivation therapy (ADT) plus docetaxel or abiraterone, which offers a survival benefit over ADT alone. The recommendations are based on data from the CHAARTED, LATITUDE, STAMPEDE, and GETUG-15 clinical trials.

Bristol-Myers Squibb's nivolumab (Opdivo) was shown to be active in patients with recurrent or metastatic nasopharyngeal carcinoma, as reported in the Journal of Clinical Oncology. In a phase II trial, patients treated with the drug had an objective response rate of 20.5%, a 1-year overall survival (OS) rate of 59%, and a 1-year progression-free survival (PFS) rate of 19.3%. The FDA has approved nivolumab to treat various cancers, most recently for a new indication in melanoma and for hepatocellular carcinoma.
In the phase III ECHO-301/KEYNOTE-252, epacadostat (Incyte) plus pembrolizumab (Keytruda; Merck) did not improve PFS, the primary endpoint, in patients with inoperable or metastatic melanoma, the companies announced. In addition, the trial is not expected to meet its secondary endpoint of improving OS. As a result, the study will be discontinued.
Eli Lilly's ramucirumab (Cyramza) may improve survival for patients with hepatocellular carcinoma and elevated alpha-fetoprotein. The company announced that the phase III REACH-2 trial met its primary endpoint of OS and its secondary endpoint of PFS in patients treated with the drug. Ramucirumab has FDA approval for certain forms of lung, colorectal, and gastric cancers.

March 2018

March 23–29

The FDA expanded approval of blinatumomab (Blincyto; Amgen) to include adults and children with B-cell precursor acute lymphoblastic leukemia who are in remission but still have minimal residual disease (MRD). The approval was based on results of a trial of 86 patients treated with the drug who were in their first or second complete remission with detectable MRD. Overall, 81% of patients achieved undetectable MRD, and median relapse-free survival was 22.3 months.
Gynecologic cancer research is disproportionately underfunded, researchers reported at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer in New Orleans, LA. In an analysis of funding for 13 common cancers, ovarian, cervical, and uterine cancers ranked 9th, 10th, and 12th, respectively. Ovarian cancer had a mean expenditure of $85,000 per year of life lost per 100 new cases, compared with a mean of $1.81 million for prostate cancer.
According to findings presented at the SGO meeting, the combination of AstraZeneca’s olaparib (Lynparza) and durvalumab (Imfinzi) showed activity in some patients with recurrent ovarian cancer. In the MEDIOLA phase II trial, 34 patients with relapsed, BRCA-mutated, platinum-sensitive ovarian cancer who received the combination had an objective response rate of 72% and a 12-week disease control rate of 81%. In previous studies, the combination demonstrated activity in patients with BRCA1/2-mutated HER2-negative metastatic breast cancer.

The University of Michigan Comprehensive Cancer Center received a $150 million gift from Richard and Susan Rogel, and will be renamed the University of Michigan Rogel Cancer Center. The money will support cancer research through various avenues including research grants, endowed professorships, and scholarship assistance for scientists-in-training.
Bayer's sorafenib tosylate (Nexavar) may improve survival in patients with desmoid tumors or aggressive fibromatosis, according to interim results of a phase III trial. In the study, which included 87 patients, those treated with the drug had a median progression-free survival (PFS) of 15 months, compared with a PFS of 6 months in patients who received a placebo. The drug is approved for some kidney, liver, and thyroid cancers.
Several public health organizations are suing the FDA for delaying regulation of electronic cigarettes (e-cigarettes) and cigars. The lawsuit challenges the agency’s decision to extend the deadline for manufacturers to submit product-review applications to the FDA from August 2018 to August 2021 for cigars and August 2022 for e-cigarettes. The American Academy of Pediatrics, American Cancer Society Cancer Action Network, American Heart Association, and American Lung Association are among those involved.

March 16–22

Congress approved a federal budget for fiscal year 2018 that will include a $3 billion increase for the NIH, which would bring the agency’s budget to $37.1 billion. The NCI will receive $5.965 billion, including $300 million designated for the National Cancer Moonshot Initiative through the 21st Century Cures Act. The spending bill also allocates $15 million for the FDA’s Oncology Center of Excellence.
The Centers for Medicare & Medicaid Services announced it will cover FDA-approved next-generation sequencing tests and companion diagnostics for patients with Medicare who have recurrent, relapsed, refractory, metastatic, or advanced stage III or IV cancer. One such test is FoundationOne CDx (Foundation Medicine), which can detect genetic mutations in 324 genes and two genomic signatures in any solid tumor, and match patients to one of 17 targeted therapies that treat advanced cancers.
"Right-to-try" legislation was nixed again. After defeating the measure, which would have allowed seriously ill patient access to experimental treatments, last week, the House passed it this week by a vote of 267 to 149. However, the Senate later voted it down. The bill’s lead sponsor, Senator Ron Johnson (R-WI), vowed to continue to push to have such legislation approved.
The FDA approved brentuximab vedotin (Adcetris; Seattle Genetics), in combination with chemotherapy, to treat adults with untreated stage III or IV classic Hodgkin lymphoma. The decision was based on results of the ECHELON-1 phase III clinical trial in which patients treated with the drug plus AVD chemotherapy (doxorubicin, vinblastine, and dacarbazine) had a 23% reduction in the risk of disease progression, death, or need for additional cancer treatments, compared with those who received the ABVD chemotherapy regimen (doxorubicin, bleomycin, vinblastine, and dacarbazine).

The FDA also approved nilotinib (Tasigna; Novartis) for first- and second-line treatment of Philadelphia chromosome–positive chronic myeloid leukemia in the chronic phase in children at least 1 year old. Approval was based on the results of two trials: In one, newly diagnosed patients treated with nilotinib had a cumulative major molecular response (MMR) of 64% by cycle 12; in the other, patients who developed imatinib resistance or intolerance and then received nilotinib had a cumulative MMR of 47.79% by cycle 12.
MRI screening could reduce the need for prostate biopsies and improve cancer diagnosis, according to a study in The New England Journal of Medicine. In the PRECISION1 trial, 500 men suspected of having prostate cancer either underwent MRI followed by targeted biopsy, if needed, or standard biopsy. Men in the MRI group had 28% fewer biopsies, and were more likely to be diagnosed with clinically significant cancer and less likely to be diagnosed with clinically insignificant cancer.

March 9–15

The FDA announced its intent to investigate placing a limit on nicotine levels in combustible cigarettes. “This new regulatory step advances a comprehensive policy framework that we believe could help avoid millions of tobacco-related deaths across the country,” said FDA Commissioner Scott Gottlieb, MD. The agency will review scientific research on the role of nicotine in cigarette addiction, and seek public input.
The U.S. House of Representatives failed to pass “right to try” legislation that would allow seriously ill patients access to experimental treatments. The legislation was strongly supported by President Donald Trump and Vice President Mike Pence but criticized by Democrats for weakening FDA protections. More than 75 patient groups sent a letter to legislators recommending against the bill’s passage, which was rejected by a vote of 259 to 140.
The American Association for Cancer Research (AACR) launched the “2020 by 2020” initiative to improve understanding of cancer outcomes for African-Americans. The initiative aims, by 2020, to combine genetic sequencing data from tumor and normal tissue samples from 2,020 African-American patients with their clinical records. Data will be added to the AACR’s Project GENIE database, which has thus far released deidentified genomic records from 39,600 patients to researchers.
The FDA placed a clinical hold on a phase I/II trial of axalimogene filolisbac (Advaxis) in combination with durvalumab (Imfinzi; AstraZeneca) to treat patients with advanced recurrent/refractory human papillomavirus (HPV)–associated cervical cancer and HPV-associated head and neck cancer. The hold was initiated after a patient died of respiratory failure after the sixth treatment cycle.

Prophylactic use of heart medication may reduce cardiotoxicity from cancer drugs in patients with HER2-positive breast cancer. In a trial of 468 patients, those treated with trastuzumab (Herceptin; Genentech) after receiving doxorubicin who also took the beta blocker carvedilol (Coreg; GlaxoSmithKline) or the ACE inhibitor lisinopril experienced significantly fewer cardiac events than those receiving a placebo. Findings were presented at the American College of Cardiology’s 67th Annual Scientific Session in Orlando, FL.
Chlamydia is associated with increased risk of ovarian cancer, according to findings presented during a media preview for the 2018 AACR Annual Meeting. Researchers examined data from a Polish study of women with ovarian cancer and from the NCI-sponsored Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. They established that women who had antibodies against the protein pgp3, which is a highly accurate marker for chlamydia, were twice as likely to have been diagnosed with ovarian cancer.
The FDA designated erdafitinib (Janssen) as a Breakthrough Therapy to treat metastatic urothelial cancer. Erdafitinib is an oral FGFR tyrosine kinase inhibitor. The designation is based on the results of a phase IIa clinical trial in which the drug had an overall response rate of 42% in 59 patients with relapsed/refractory disease who had certain FGFR mutations.

March 2–8

The FDA authorized the marketing of a direct-to-consumer test for BRCA1/2 breast cancer mutations. The test, which will be sold by genetics company 23andMe, can detect three BRCA1/2 mutations associated with a higher risk of developing breast, ovarian, and prostate cancers. The mutations occur in roughly 2% of Ashkenazi Jewish women, but are rare in other ethnic groups.
Merck paid $300 million up front to partner with Japanese pharmaceutical company Eisai in a deal that could be worth up to $5.76 billion for Eisai. Merck will develop and sell Eisai’s lenvatinib (Lenvima), an FDA-approved multikinase inhibitor to treat thyroid cancer, and to treat renal cell carcinoma (RCC) in combination with everolimus (Afinitor; Novartis). The FDA also designated lenvatinib as a Breakthrough Therapy to treat RCC in combination with pembrolizumab (Keytruda; Merck).
Oncologists may be prescribing drugs for some indications based upon weak evidence, according to a study in the BMJ. Researchers examined 47 new cancer drugs approved by the FDA between 2011 and 2015, and found the FDA authorized the drugs for 69 indications, whereas the NCCN recommended these drugs for 113 indications. The additional indications recommended by the NCCN were largely based on small, uncontrolled studies, case reports, or no evidence, the researchers reported.

Current guidelines that recommend starting mammographic breast cancer screening at age 50 may lead to delayed diagnosis in nonwhite women, according to a report published in JAMA Surgery. Researchers analyzed racial differences in age and tumor stage at the time of diagnosis and found that, compared with white women, higher percentages of black, Hispanic, and Asian women were diagnosed before age 50, and higher percentages of black and Hispanic patients were diagnosed with advanced cancers.
British Prime Minister Theresa May called for the UK to remain part of the European Medicines Agency (EMA) after Brexit. “Membership of the [EMA] would mean investment in new innovative medicines continuing in the UK, and it would mean these medicines getting to patients faster as firms prioritize larger markets when they start the lengthy process of seeking authorizations. But it would also be good for the EU because the UK regulator assesses more new medicines than any other member state. And the EU would continue to access the expertise of the UK’s world-leading universities,” she said in a speech.
Celgene paid $101 million to collaborate with biotechnology company Vividion for the next 4 years. Vividion is known for its ubiquitin proteasome system that breaks down proteins, and will attempt to apply the system to hard-to-drug protein targets for various diseases, including cancers. In the deal, Vividion will develop and identify investigational new drugs that Celgene will move into clinical trials.

February 2018

February 23–March 1

The FDA approved abemaciclib (Verzenio; Eli Lilly) as a first-line endocrine-based therapy for postmenopausal women with HR-positive/HER2-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor. In the phase III MONARCH 3 trial, women treated with the drug had a median progression-free survival of 28.2 months, versus 14.8 months in women who received a placebo. The FDA approved abemaciclib in 2017 for patients whose breast cancer progressed after endocrine therapy.
The National Science Foundation (NSF) announced it will close three overseas offices—in Beijing, China; Brussels, Belgium; and Tokyo, Japan—by this summer. The NSF opened the Tokyo office in 1960, established a European office in Paris in 1984 that relocated to Brussels 3 years ago, and set up the Beijing office in 2006. Rebecca Keiser, head of the NSF’s international office, told Science that the decision was based on the agency’s desire to be “more strategic and focused” in its international affairs.
Europe’s Committee for Medicinal Products for Human Use (CHMP) recommended approval of four cancer drugs: gemtuzumab ozogamicin (Mylotarg; Pfizer) for previously untreated, CD33-positive acute myeloid leukemia; bosutinib (Bosulif; Pfizer) as a first-line therapy for chronic-phase Philadelphia chromosome–positive chronic myelogenous leukemia; olaparib (Lynparza; AstraZeneca) as a maintenance therapy for patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer; and rucaparib (Rubraca; Clovis Oncology) for women with advanced BRCA-mutant ovarian cancer. The European Commission will make the final approval decision.
In addition, the CHMP recommended against approving two cancer drugs: neratinib (Nerlynx; Puma Biotechnology) for the extended adjuvant treatment of patients with early-stage HER2-positive breast cancer, and sunitinib (Sutent; Pfizer) for adjuvant use for kidney cancer.

In 2016, 7.2% of women who gave birth smoked cigarettes during pregnancy, according to a report from the Centers for Disease Control and Prevention. Smoking prevalence varied by state, ranging from 1.6% in California to 25.1% in West Virginia, and also varied based on maternal age, race, and educational level: Young and less educated mothers were more likely to continue smoking while pregnant.
The FDA designated YS-ON-001 (Yisheng Biopharma) an Orphan Drug for the treatment of pancreatic cancer. The agent is being studied in a phase I clinical trial of patients with the disease and a variety of other advanced solid tumors. YS-ON-001, which can induce antitumor cytokines, activate natural killer cells, and suppress regulatory T cells, received Orphan Drug designation for hepatocellular carcinoma in 2016.
Scientists discovered the earliest known images of malignant breast cancer in two 16th-century Renaissance paintings: “The Night,” by Michele di Rodolfo del Ghirlandaio, and “The Allegory of Fortitude,” by Maso di San Friano. Although advancements in breast surgery were made during this period, mastectomy was relatively uncommon, the researchers wrote, “resulting in high numbers of visible, advanced breast cancers.”

February 16–22

The FDA expanded the indication for durvalumab (Imfinzi; AstraZeneca) to include the treatment of patients with inoperable stage III non–small cell lung cancer whose cancer has not progressed after chemoradiation. It is the first approved treatment for the disease to reduce the risk of cancer progression. The decision was based on results of a phase III trial in which 473 patients treated with durvalumab had a median progression-free survival of 16.8 months compared with 5.6 months in 236 patients who received a placebo.
Contrary to recommendations from other organizations, the American Cancer Society (ACS) endorsed the use of electronic cigarettes (e-cigarettes) to aid in smoking cessation among smokers who will not use FDA-approved cessation products, such as nicotine gum and patches. According to the ACS’s policy statement, “these individuals should be encouraged to switch to the least harmful form of tobacco product possible; switching to the exclusive use of e-cigarettes is preferable to continuing to smoke combustible products.” However, the statement goes on to say that “these individuals should be regularly advised to completely quit using all tobacco products,” including e-cigarettes.

Larotrectinib (LOXO-101; Loxo Oncology) is safe and effective for patients with various cancers, according to data from three clinical trials published in The New England Journal of Medicine. In total, 55 patients between 4 months and 76 years old with 17 different TRK fusion–positive cancers who received the drug had an overall response rate of 75% and experienced minimal side effects. The FDA designated larotrectinib as an Orphan Drug in 2017.
Gilead subsidiary Kite Pharma announced that it will collaborate with Sangamo Therapeutics, a deal that could net Sangamo up to $3 billion in milestone payments. Kite will use Sangamo’s zinc finger nuclease platform to modify genes as it develops next-generation cell therapies for autologous and allogeneic use in treating various cancers.
Merck announced that it will acquire the Australian biotechnology company Viralytics for $394 million. Viralytics develops oncolytic immunotherapies. Its leading product, Cavatak, is a proprietary formulation of an oncolytic virus (coxsackievirus). Cavatak is being evaluated in phase I and II clinical trials to treat melanoma and prostate, lung, and bladder cancers as a monotherapy, as well as in combination with the PD-1 inhibitor pembrolizumab (Keytruda; Merck).

February 9–15

Congress passed the Bipartisan Budget Agreement Act of 2018, which increases defense and nondefense discretionary caps by a total of $300 billion over the next two fiscal years. The NIH stands to benefit from the $131 billion increase in nondefense discretionary spending if the funds allow the $2 billion increase the Senate Appropriations Committee approved for the agency in 2017 to become a reality.
The White House issued its budget proposal for fiscal year (FY) 2019, which includes a $400 million increase for the FDA, $20 million of which would go to the Oncology Center of Excellence. The proposal cuts the NCI budget by $24 million compared with FY2017, and sets the NIH budget at $35.5 billion, which, with medical inflation, is essentially a budget cut.
Roche will buy cancer technology startup Flatiron Health for $1.9 billion. Flatiron Health, which has previously partnered with the FDA and Cambridge, MA–based Foundation Medicine, creates software for oncology-focused electronic health records (EHR). At the 2017 American Society of Clinical Oncology Annual Meeting, Flatiron and Foundation Medicine presented their joint Clinico-Genomic Database, which integrates patient clinical data—including diagnosis, treatment, and outcomes—from Flatiron’s EHR data platform with detailed genomic data from Foundation Medicine’s registry of more than 100,000 patients.

Bristol-Meyers Squibb will pay $1.85 billion to Nektar Therapeutics for rights to the experimental cancer drug NKTR-214. In the deal, Bristol will get 35% of global profits should the drug reach market, and the exclusive right to combine the drug with its PD-1 inhibitor nivolumab (Opdivo) and CTLA4 inhibitor ipilimumab (Yervoy). NKTR-214 is designed to expand cancer-fighting T cells and natural killer cells in the tumor microenvironment.
The combination of axitinib (Inlyta; Pfizer) and pembrolizumab (Keytruda; Merck) showed high clinical activity in patients with newly diagnosed advanced renal cell carcinoma. In a phase Ib clinical trial, patients treated with the combination had an objective response rate of 73.1% and a median duration of response of 18.6 months. Results were presented at the 2018 Genitourinary Cancers Symposium and published concurrently in The Lancet Oncology.
The U.S Preventive Services Task Force recommended against screening for ovarian cancer in women without symptoms who aren’t at high genetic risk for the disease, concluding that screening does not reduce mortality and can be associated with moderate to substantial harms. The recommendation has not changed since 2012, but now incorporates additional evidence from the UK Collaborative Trial of Ovarian Cancer Screening.

February 2–8

PP2A inhibitors combined with the tyrosine kinase inhibitor (TKI) imatinib mesylate (Gleevec) improved survival in mouse models of malignant BCR–ABL+ leukemia. The study in Science Translational Medicine also found the combination killed blood cancer progenitor cells taken at diagnosis from human patients with leukemia who were later classified as TKI nonresponders, while sparing healthy bone marrow.
The amino acid asparagine may play a role in the spread of triple-negative breast cancer, according to a study in Nature. Researchers found that limiting asparagine in mice through reduction of asparagine synthetase, treatment with L-asparaginase, or dietary restriction limited the ability of the cancer to travel to different parts of the body. When mice were given asparagine-rich food, cancer cells spread more quickly.
The combination of encorafenib and binimetinib (Array BioPharma Inc.) improved outcomes in patients with BRAF-mutant melanoma. In the COLUMBUS phase III trial, patients treated with the combination had a median overall survival of 33.6 months, compared with a median overall survival of 16.9 months in patients treated with vemurafenib (Zelboraf; Roche). The FDA will make an approval decision about the drugs by June 30.
Sunday, February 4, was World Cancer Day, an initiative of the Union for International Cancer Control (UICC). Around the world, communities held festivals, walks, seminars, public information campaigns, and other events to raise awareness about cancer issues. On February 3 the Empire State Building was lit in orange and blue, the colors of the UICC.

Celgene Corporation announced positive results in a trial of pomalidomide (Pomalyst/Imnovid) plus bortezomib and low-dose dexamethasone (PVD) to treat patients with relapsed/refractory multiple myeloma. In the OPTIMISMM phase III clinical trial, patients treated with the combination had a statistically significant improvement in progression-free survival compared with patients treated with bortezomib and low-dose dexamethasone.
The American Society of Clinical Oncology released a clinical practice guideline on treatment of malignant pleural mesothelioma. The guideline was created based on an expert panel review of 222 studies published between 1990 and 2017. It provides detailed recommendations on diagnosis, staging, and treatment, including recommendations on chemotherapy, cytoreductive surgery, and radiation therapy.
The FDA approved abiraterone acetate (Zytiga) in combination with prednisone to treat patients with metastatic high-risk castration-sensitive prostate cancer. In the LATITUDE phase III trial, patients treated with the combination did not reach median overall survival, compared with a median overall survival of 34.7 months in patients who received a placebo. The FDA approved abiraterone acetate with prednisone in 2011 for patients with metastatic castration-resistant prostate cancer who received prior chemotherapy, and expanded the indication in 2012 to patients with metastatic castration-resistant prostate cancer.

January 2018

January 26–February 1

The FDA approved lutetium Lu 177 dotatate (Lutathera; Novartis, Advanced Accelerator Applications) to treat somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors. Approval was based on results of two studies: In the NETTER-1 phase III clinical trial of 229 patients, those who received the drug in combination with octreotide had longer progression-free survival than those who received octreotide alone (65.2% vs. 10.8% at 20 months, respectively). In another study, 16% of 360 patients treated with lutetium Lu 177 dotatate had complete or partial tumor shrinkage.
Varian Medical Systems agreed to buy Sirtex Medical, a company that specializes in liver cancer therapies, for $1.3 billion. Sirtex’s SIR-Spheres Y-90 resin microspheres device uses radioactive beads to target liver tumors with high doses of radiation. SIR-Spheres received FDA premarket approval in 2002 to treat colorectal cancer that has spread to the liver.
As part of its “Convergence 2.0” research initiative, Stand Up To Cancer awarded $11 million to seven interdisciplinary research teams to investigate how the immune system responds to cancer. Teams consisting of experts in life sciences, physical sciences, mathematics, and engineering will collaborate with machine learning experts at Microsoft, using terabytes of patient data to analyze interactions between the immune system and cancer with the goal of advancing cancer therapies.

The FDA placed a clinical hold on four phase I/II trials of BPX-501 (Bellicum Pharmaceuticals) after three patients developed encephalopathy possibly related to the drug. BPX-501 was developed to improve treatment outcomes in patients undergoing haploidentical hematopoietic stem cell transplants for a variety of diseases, including leukemias, lymphomas, and genetic blood diseases. The FDA designated it as an Orphan Drug in 2016.
Breast cancer treatments like chemotherapy and radiation can have a negative impact on cardiovascular health in women, the American Heart Association warned. The scientific statement, published in Circulation, provides an overview of prevalence, shared risk factors, and cardiotoxic effects of cancer therapy, and prevention and treatment of cardiovascular disease in patients with breast cancer. It also highlights the need for research on the overlap between the diseases, and calls for greater collaboration between cardiologists and oncologists when treating patients.
Deaths caused by liver cancer have increased by 80% over the last 26 years, a comprehensive, global epidemiologic study revealed. The analysis showed that 830,000 people died from the disease in 2016, compared with 464,000 deaths in 1990. Primary liver cancer, the most prevalent type, is most commonly caused by long-term infection with hepatitis B or hepatitis C virus.

January 19–25

Celgene acquired Juno Therapeutics for $9 billion. The deal will give Celgene access to Juno’s chimeric antigen receptor (CAR) T-cell therapies, including JCAR017, which earned Breakthrough Therapy designation from the FDA in 2016 to treat patients with relapsed/refractory, aggressive large B-cell non-Hodgkin lymphoma. Earlier this month, Celgene bought Impact Biomedicines for $1.1 billion up front, with additional payments for reaching milestones that could bring the cost to nearly $7 billion.
Bristol-Myers Squibb’s PD-1 inhibitor nivolumab (Opdivo) combined with its CTLA4 inhibitor ipilimumab (Yervoy) demonstrated clinical activity in patients with DNA mismatch repair–deficient or microsatellite instability–high metastatic colorectal cancer. In the ongoing phase II CheckMate-142 trial, the objective response rate was 55%, and 85% of patients treated with the combination survived 1 year. The data were presented at the 2018 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in San Francisco, CA.
ChemoCentryx announced positive overall survival (OS) results in an ongoing phase Ib clinical trial of its CCR2 inhibitor CCX872 for treating locally advanced/metastatic pancreatic cancer. Fifty patients treated with CCX872 in combination with FOLFIRINOX, a four-drug chemotherapy regimen, had an OS of 29% at 18 months, compared with a previously published OS of 18.6% at 18 months in patients treated with FOLFIRINOX alone based on results from a phase II/III clinical trial. Findings will be presented at the 2018 ASCO Clinical Immuno-Oncology Symposium in San Francisco, CA.

The newly launched biotech Tmunity is raising $100 million from investors, in part to fund two clinical trials on T-cell therapies for treating solid tumors. The company’s CAR T therapy will target prostate-specific membrane antigen in patients with prostate cancer, whereas a second study will use CRISPR to edit T-cell DNA. The Parker Institute for Cancer Immunotherapy, Gilead Sciences, and Ping An Investors, among others, will fund the venture.
Researchers discovered that postmenopausal women with ER-positive breast cancer who have high intratumor heterogeneity of estrogen receptors have twice the risk of death from the disease as patients with low intratumor heterogeneity. The study, published in the Journal of the National Cancer Institute, followed 573 women diagnosed between 1976 and 1990 who received either tamoxifen or no systemic therapy after surgery. Their findings also held true for women with luminal A subtype tumors, which are generally considered to be low risk.
A report from the U.S. National Academies of Sciences, Engineering, and Medicine concluded that electronic cigarettes (e-cigarettes), although addictive, are less toxic than conventional cigarettes. The findings were based on a comprehensive review of more than 800 studies on the battery-powered devices. However, the report’s authors say that more research is needed to understand the long-term health effects of e-cigarettes, their utility as a smoking cessation tool, and the role they play in hooking adolescents on conventional cigarettes.

January 12–18

Researchers announced the development of a single blood test that screens for eight common cancers by evaluating levels of certain cancer proteins and the presence of gene mutations from circulating DNA. Five of the cancers covered by the test–ovarian, liver, stomach, pancreatic, and esophageal cancers–currently have no screening test. Dubbed CancerSEEK, the test can also screen for colorectal, lung, and breast cancers.
Novartis announced that the FDA granted Priority Review for tisagenlecleucel (Kymriah) for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma. Tisagenlecleucel was the first chimeric antigen receptor (CAR) T-cell therapy greenlighted by the agency when it was approved in August for certain patients with B-cell precursor acute lymphoblastic leukemia.
Having just merged, Kite Pharma and Gilead announced that they will team up with Pfizer to study the use of their CAR T-cell therapy axicabtagene ciloleucel (Yescarta) with Pfizer’s utomilumab in certain blood cancers. Axicabtagene ciloleucel was approved last year for relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. Utomilumab, an experimental humanized 4-1BB agonist, has shown enhanced T-cell mediated immune responses in preclinical models.

Cambridge, MA–based Foundation Medicine announced that the company will partner with Pfizer to develop companion diagnostics for Pfizer’s cancer therapies. The new tests will be included in updates to the FoundationOne CDX, which was recently approved as a companion diagnostic for patients with certain types of non–small cell lung cancer (NSCLC), melanoma, and colorectal, ovarian, and breast cancers to identify those who may benefit from one of 17 approved targeted therapies.
In the largest study to date using dental exams instead of self-reporting from patients, researchers found a 24% increase in the risk of developing cancer among people with severe periodontitis. The Atherosclerosis Risk in Communities study, which followed 7,466 participants from the late 1990s until 2012, concluded that the highest risk was observed in cases of lung cancer, followed by colorectal cancer. The researchers noted that additional research is needed to determine whether prevention and treatment of periodontal disease can alleviate the cancer risk.
The FDA broadened the indication for afatinib (Gilotrif; Boehringer Ingelheim) to include first-line treatment of patients with metastatic NSCLC whose tumors have nonresistant EGFR mutations (S768I, L861Q, and/or G719X) other than exon 19 deletions or exon 21 L858R substitutions. Afatinib was initially approved in 2013. Qiagen said that the agency also extended the indications for its Therascreen EGFR RGQ PCR kit to guide the drug’s use.

January 5–11

The FDA approved olaparib (Lynparza) to treat patients with germline BRCA-mutated HER2-negative metastatic breast cancer who have previously received chemotherapy. Approval was based on results of the OlympiA phase III clinical trial, where the drug increased median progression-free survival from 4.2 months to 7 months. Olaparib, the first PARP inhibitor approved to treat breast cancer, received FDA approval in 2014 to treat certain patients with ovarian cancer. The agency also expanded approval of the BRACAnalysis CDx, a companion test for olaparib, to include patients with breast cancer.
Celgene acquired biotech startup Impact Biomedicines for $1.1 billion up front, and it could pay another $6 billion if Impact meets regulatory milestones and sales goals. Celgene is known for its cancer drugs, most notably lenalidomide (Revlimid), which treats multiple myeloma and myelodysplastic syndromes. Celgene will gain access to Impact’s drug fedratinib, development of which was halted in 2013 due to adverse side effects. Last year, the FDA granted permission for continued testing.
India’s supreme court suspended a lower court’s order to eliminate federal rules requiring larger health warnings on tobacco packages, as reported in Reuters. Current packaging rules, which have been in effect since 2016 and are among the strictest in the world, mandate that 85% of tobacco packaging be covered with health warnings. In its decision, the supreme court highlighted the need to protect the health of citizens: The government estimates that every year, more than 900,000 people in India die from tobacco-related illnesses, but a 2016 government survey found that 62% of smokers consider quitting because of such health warnings on packaging.

A gene expression profile test that helps predict the recurrence of breast cancer, Oncotype DX, may be less cost-effective under real-world conditions than originally thought, according to a study in the Journal of Clinical Oncology. The test was previously shown to be cost-effective under ideal conditions—all patients tested, test score used to inform treatment decisions, and perfect prediction of recurrence. In the new study, researchers found that in community practice, the cost-effectiveness ratio for testing versus usual care without testing was $188,125 per quality-adjusted life-year (QALY), almost five times the ratio of $39,496 per QALY under ideal conditions.
Researchers identified a possible biomarker of response to anti–PD-1 therapy in patients with melanoma. They conducted a detailed analysis of the immune cell subsets in the peripheral blood of patients with stage IV melanoma before and after 12 weeks of treatment. They found that the frequency of CD14⁺CD16⁻HLA⁻DR^hi monocytes was a strong predictor of treatment success.
A genetic tool may be able to predict when men will develop aggressive prostate cancer and help guide screening decisions. Researchers analyzed over 200,000 gene variants from 31,747 men with and without prostate cancer, and used 54 variants associated with increased risk to build a predictive model. They found that the hazard scores calculated by the model for 6,411 men enrolled in an independent study were a highly significant predictor of age at diagnosis, and that men with scores in the top 2% were three times more likely to develop aggressive prostate cancer than men at average risk.

Noted This Week - 2018 Archive

December 2018

December 21, 2018–January 3, 2019

Earlier This Year:

Noted This Week Archive:

December 14–20

December 7–13

November 30–December 6

November 2018

November 21–29

November 16–20

November 9–15

November 2–8

October 2018

October 26–November 1

October 19–25

October 12–18

October 5–11

September 28–October 4

September 2018

September 21–27

September 14–20

September 7–13

August 31–September 6

August 2018

August 24–30

August 17–23

August 10–16

August 3–9

July 2018

July 27–August 2

July 20–26

July 13–19

July 6–12

June 29–July 5

June 2018

June 22–28

June 15–21

June 8–14

June 1–7

May 2018

May 25–31

May 18–24

May 11–17

May 4–10

April 2018

April 27–May 3

April 20–26

April 13–19 This Week: Special Content from the American Association for Cancer Research’s (AACR) Annual Meeting 2018 and other news

April 6–12

March 30–April 5

March 2018

March 23–29

March 16–22

March 9–15

March 2–8

February 2018

February 23–March 1

February 16–22

February 9–15

February 2–8

January 2018

January 26–February 1

January 19–25

January 12–18

January 5–11

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This Week: Special Content from the American Association for Cancer Research’s (AACR) Annual Meeting 2018 and other news