Phase III trials combining bevacizumab with chemotherapy extended survival for patients with relapsed ovarian and colorectal cancer and showed that tumors that become resistant to chemotherapy do not necessarily become resistant to antiangiogenic therapy.
Phase III trials combine antiangiogenic drug with chemotherapy in relapsed and advanced disease.
Combination therapies that include bevacizumab (Avastin; Genentech) extend progression-free survival for patients with ovarian and colorectal cancers that have relapsed, expanding the pool of possible treatment options for patients with these diseases, researchers say. Findings from 2 recent European phase III studies were presented at the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO), held in Chicago from June 1–5.
In the ovarian cancer trial, dubbed AURELIA, the investigators found that adding bevacizumab, a VEGF inhibitor, to standard chemotherapy doubled the duration of progression-free survival (PFS) in women whose disease had become resistant to platinum-based therapies.
Platinum resistance affects about 1 in 4 patients with ovarian cancer, said lead investigator Eric Pujade-Lauraine, MD, PhD, of the Hôpital Hôtel-Dieu in Paris. “These patients, before now, haven't had that many treatment options open to them,” he pointed out.
The AURELIA study randomly assigned 361 patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer whose disease progressed within 6 months of their last dose of platinum therapy to receive bevacizumab and chemotherapy or chemotherapy alone. The patients received 1 of 3 equally effective standard chemotherapy drugs—liposomal pegylated doxorubicin, topotecan, or paclitaxel.
After a median follow-up of 13.5 months, 75% of the patients who received bevacizumab in addition to chemotherapy experienced disease recurrence, compared with 91% of the patients who received chemotherapy alone. The median progression-free survival among patients who received the drug combination was 6.7 months, compared with 3.4 months for patients in the chemotherapy-only group.
“For the first time in platinum-resistant ovarian cancer, we have been able to significantly improve progression-free survival with a combination therapy,” said Pujade-Lauraine, adding that the combination therapy should be considered a new standard option. For a woman with platinum-resistant ovarian cancer, “this will give her new hope,” he added.
Another phase III clinical trial involving bevacizumab yielded similarly optimistic findings for patients with advanced colorectal cancer. In this trial, 820 patients with metastatic, inoperable disease were treated with standard first-line chemotherapy (oxaliplatin or irinotecan) and bevacizumab. Following disease progression, the patients were randomly assigned to receive the other chemotherapy plus either bevacizumab or a placebo. Researchers found that both overall survival (11.2 months vs. 9.8 months) and progression-free survival (5.7 months vs. 4.1 months) were significantly longer among patients who received continual bevacizumab—with few additional side effects.
This is the first randomized trial to evaluate the combination regimen for second-line use in patients who had previously been treated with a bevacizumab regimen in the first-line setting. Its results validate the treatment approach that many U.S. oncologists already advocate and may change the standard of care in other parts of the world, where the use of bevacizumab is generally restricted to either first- or second-line treatment, not both.
“The findings also provide an important new insight about the biology of advanced colorectal cancer, showing us that if the disease develops resistance to chemotherapy, it does not necessarily mean that tumors become resistant to antiangiogenic therapy,” said Dirk Arnold, MD, director of the Hubertus Wald Tumor Center at the University Cancer Center in Hamburg, Germany, and spokesperson for the German AIO Colorectal Cancer Collaborative Study Group, which initiated the trial.
“By simply switching chemotherapy drugs when the cancer progresses and continuing with bevacizumab, we can make second-line treatment even more powerful,” Arnold added. “This finding will likely spur research into other cancer types that are sensitive to both bevacizumab and chemotherapy.”