Ten-year follow up from the CheckMate 067 and KEYNOTE-006 trials confirm that patients with advanced melanoma can achieve durable responses from treatment with the PD1 inhibitors nivolumab and pembrolizumab and that a lack of disease progression at 3 years is strong indicator of long-term survival. Dual checkpoint inhibition offers the deepest response, but monotherapy may be appropriate when aiming to avoid side effects.

NVL-655, a fourth generation ALK tyrosine kinase inhibitor, was effective and well tolerated in the ALKOVE-1 trial in patients with ALK -positive non–small cell lung cancer that had previously been treated with earlier-generation ALK inhibitors, including lorlatinib.

The monoclonal antibody ponsegromab, which inhibits the cytokine GDF-15, led to improvements in weight gain, appetite, and physical activity compared to placebo in patients with cancer cachexia across multiple cancer types and in all dose groups. The findings suggest that GDF-15 is heavily involved in cachexia, and that ponsegromab is a promising therapeutic avenue for treating it.

The development of second-generation covalent “off”-state KRAS G12C inhibitors is taking off. Two candidates, D3S-001 and divarasib, highlighted at the 2024 ESMO Congress, show better efficacy, with good tolerability, in non–small cell lung cancer as well as in colorectal cancer, against which the activity of first-generation inhibitors has been underwhelming.

The tumor-selective PRMT5 inhibitor AMG 193 showed promising safety and antitumor activity in non–small cell lung, pancreatic, and biliary duct cancer. Grade 3 or higher adverse events were low, and partial responses were seen across cancer types, supporting further trials for this and other MTA-cooperative PRMT5 inhibitors.

Data from the phase I KN-8701 trial suggest that combining exarafenib, an investigational pan-RAF inhibitor, with the MEK agent binimetinib is a reasonable second-line option for NRAS -mutant melanoma. Meanwhile, in a substudy of the phase I/II FIRELIGHT-1 trial, the type II RAF inhibitor tovorafenib appears active against not only RAF fusion-positive relapsed/refractory melanoma, but central nervous system tumors as well.

Zhijian ‘James’ Chen, PhD, has been awarded the Albert Lasker Basic Medical Research Award for his 2012 discovery of how the cGAS-STING pathway senses cytosolic DNA to trigger immune responses. This research swiftly paved the way for the development of drug candidates aimed at enhancing anti-tumor immunity, with more than a dozen STING agonists now in human testing.

Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab showed significant improvements in overall survival compared with placebo plus chemotherapy in patients with high-risk, early-stage triple-negative breast cancer. The findings, derived from the KEYSTONE-522 trial, strongly support using this pembrolizumab regimen as the standard-of-care therapy for this difficult-to-treat disease.

CDK2 inhibitors have received some attention at the 2024 ESMO Congress, with one candidate, PF-07104091, showing combination potential with CDK4-selective blockade in HR–positive, HER2–negative breast cancer, and another, INCB123667, looking active in ovarian cancer. When it comes to inhibiting ATR, a retrospective analysis points toward the allelic status of ATM LOF tumors as a biomarker that could predict which patients are likely to benefit.

Adding the PD-1 inhibitor pembrolizumab to chemoradiotherapy for high-risk, locally advanced cervical cancer significantly improves patients’ overall survival compared to treatment with CRT alone. Determining the optimal duration of pembrolizumab treatment is crucial for controlling the cost of treatment.

A significant association was found between short-term exposure to PM 2.5 and EGFR mutations in females with lung cancer, suggesting that air pollution may promote lung cancer by mutating EGFR in these individuals.

A new study finds that clinical trials are more likely to stop early if there is no genetic evidence for the treatment. Insufficient patient enrollment is the main cause for early termination in trials overall. But the results show that cancer trials are more likely to end prematurely because of safety concerns.

Results from the NeoCOAST-2 trial and a comparison of the Checkmate 77T trial and Checkmate 816 trial indicate that treatment of NSCLC with antibody-drug conjugates before and after surgery improves risk of disease recurrence compared with adjuvant therapy alone. More research is needed to understand exactly how PD-L1 expression among patients affects how patients fare, as the gene’s expression improved outcomes in NeoCOAST-2 trial but not in the Checkmate trials.

Two HER2-targeted tyrosine kinase inhibitors, BAY 29270078 and zongertinib, each showed robust efficacy and safety in early phase. Patients experienced significant tumor shrinkage rates, and the incidence of serious adverse events was low in both trials.

Combination therapy with the EGFR inhibitor osimertinib and the MET tyrosine kinase inhibitor savolitinib significantly improves outcomes for patients with EGFR -mutant, MET -aberrant non–small cell lung cancer compared with osimertinib monotherapy. However, future studies including a cohort of patients with EGFR but not MET mutations are needed to definitively determine whether MET aberrance is an indicator of poor prognosis.

Cancer drug shortages continue to disrupt care for children, underscoring vulnerabilities in the pharmaceutical supply chain. Economic pressures on drug manufacturers highlight the need for more effective policies and collaboration among healthcare providers, pharmaceutical companies, and policymakers.

Abstract: A novel immune-oncology strategy that involves reprogramming cancer cells into functional dendritic cells directly in the body elicits strong immune responses and complete tumor regression in mice. The approach, which uses adenoviral vectors to deliver transcription factors into tumors, is expected to enter human testing in the next few years.

Abstract: The FDA’s approval of vorasidenib for IDH -mutant low-grade gliomas offers the first systemic therapy for these patients, potentially delaying more aggressive treatments. This targeted approach could balance the need for tumor control with quality-of-life considerations.

The future of cancer research priorities in the United States, particularly the Cancer Moonshot initiative, hangs in the balance with the forthcoming election. Depending on the winner, such programs could either receive continued support and potential funding boosts or face diminished federal backing, reflecting wider concerns over political influence on scientific research.

Researchers at the AI-powered pathology company Paige unveiled the second generation of Virchow, a cancer-detection model built on the largest digital pathology dataset assembled to date, demonstrating a high degree of accuracy in diagnosing cancer, discerning tumor subtypes, and predicting the status of genomic biomarkers.