“This research proves that there are new options for patients with metastatic cervical cancer,” said Bradley J. Monk, MD, gynecologic oncologist and director of the Division of Gynecologic Oncology at St. Joseph’s Hospital and Medical Center, in Phoenix, AZ, and the study’s senior author. “I predict that adding bevacizumab to chemotherapy will become the new standard of care.”
Fewer Discontinuations for Recurrence, More for Adverse Events
The study treatment was discontinued by 97% of patients. Disease progression was the reason for discontinuation in 51% of those in the chemotherapy-alone groups and 38% in the chemotherapy plus bevacizumab groups, whereas intolerable adverse events (AEs) were the reason in 16% of patients who received chemotherapy alone and 25% of those who received chemotherapy plus bevacizumab.
AEs that occurred significantly more often in the bevacizumab-treated patients were hypertension (25% vs 2%; P < 0.001), gastrointestinal or genitourinary fistulas (6% vs 0%; P = 0.002), and thromboembolic events (8% vs 1%; P = 0.001). The frequency of grade 4 or higher neutropenia, grade 3 or higher febrile neutropenia, and grade 2 or higher pain did not differ between treatment groups. Fatal AEs occurred in four patients who were given bevacizumab and four who were not.
With the increasing use of human papillomavirus vaccine, the incidence of cervical cancer is expected to decline. However, among populations in the United States and abroad without access to health care, it remains a significant problem, with 500,000 new cases and 250,000 deaths annually worldwide.
“There has been a large unmet medical need for active treatments for cervical cancer,” Dr. Monk said. “We believe the results of this study are a significant step forward and now we will move to trying to add bevacizumab to a front-line treatment when cancers are more curable, rather than using it at the time of recurrence.”
Currently, bevacizumab is approved for use against metastatic colorectal cancer, advanced nonsquamous non-small cell lung cancer, metastatic kidney cancer, and glioblastoma.
Don S. Dizon, MD, FACP
The management of women with advanced or recurrent cervical cancer continues to be a very difficult clinical scenario. Unfortunately, prior randomized clinical trials have not been able to show any clinically significant improvement in survival endpoints, despite our efforts in studying platinum-based combinations beyond cisplatin plus paclitaxel.
Taking this context into account, the findings from the Gynecologic Oncology Group (GOG) 240 trial published in the New England Journal of Medicine achieve an important milestone. For the first time, we have added an additional agent, bevacizumab, to chemotherapy and have shown that doing so improves the all-important endpoint of overall survival, in addition to a higher response rate and longer progression-free survival.
While important, this study also illustrates the disparities evident in cancer care, both within the United States and internationally. The burden of cervical cancer is greatest in resource-poor regions, where screening programs have not been practical. It raises the question, if these areas cannot afford pap smears, how are the women in these countries ever going to have access to bevacizumab?
These are important questions to ask as we address the burden of cancer globally. Still, this study is the first to demonstrate improvement in overall survival over standard of care. As such, it will have wide ranging applications to these patients and I applaud the GOG for carrying out this important clinical trial.
Don S. Dizon, MD, FACP
Gillette Center for Gynecologic Oncology
Director, Oncology Sexual Health Clinic
Massachusetts General Hospital Cancer Center
- Tewari KS, Sill MW, Long HJ 3rd, et al. Improved survival with bevacizumab in advanced cervical cancer. New Engl J Med. 2014;370(8):734-743.