Promising Results of GOG Study with Bevacizumab for Advanced Cervical Cancer

Addition of bevacizumab to combination chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer associated with improved overall survival

Patients who received bevacizumab combined with chemotherapy lived approximately 4 months longer from those who received chemotherapy alone. The study results were published in February 20, 2014 issue of the New England Journal of Medicine. The study results are important as there is a large unmet medical need for active treatments for cervical cancer.

Targeting VEGF

Vascular endothelial growth factor (VEGF) promotes angiogenesis, a mediator of disease progression in cervical cancer. Bevacizumab, a humanized anti-VEGF monoclonal antibody, has single-agent activity in previously treated, recurrent disease.

Most patients in whom recurrent cervical cancer develops have previously received cisplatin with radiation therapy, which reduces the effectiveness of cisplatin at the time of recurrence. In this study, the researchers evaluated the effectiveness of bevacizumab and non-platinum combination chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer.

The GOG 240 study

The research was conducted between April 2009 and January 2012. Using a 2-by-2 factorial design, they randomly assigned 452 patients, from 164 institutions in the United States and Spain, to chemotherapy with or without bevacizumab. Chemotherapy consisted of cisplatin plus paclitaxel or topotecan plus paclitaxel. Cycles were repeated every 21 days until disease progression, the development of unacceptable toxic effects, or a complete response was documented.

The primary endpoint was overall survival; a reduction of 30% in the hazard ratio for death was considered clinically important.

Groups were well balanced with respect to age, histologic findings, performance status, previous use or non-use of a radiosensitizing platinum agent, and disease status.
Topotecan–paclitaxel was not superior to cisplatin–paclitaxel (hazard ratio for death, 1.20). With the data for the two chemotherapy regimens combined, the addition of bevacizumab to chemotherapy was associated with increased overall survival (17.0 months vs. 13.3 months; hazard ratio for death, 0.71; p = 0.004 in a one-sided test) and higher response rates (48% vs. 36%, p = 0.008).

Bevacizumab, as compared with chemotherapy alone, was associated with an increased incidence of hypertension of grade 2 or higher (25% vs. 2%), thromboembolic events of grade 3 or higher (8% vs. 1%), and gastrointestinal fistulas of grade 3 or higher (3% vs. 0%).

The authors concluded that addition of bevacizumab to combination chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer was associated with an improvement of 3.7 months in median overall survival.

The study was funded by the National Cancer Institute (USA).

The GOG 240 study ClinicalTrials.gov number is NCT00803062.

The study results were presented in part at the 2013 Annual Meeting of the Society of Gynecologic Oncology, Los Angeles, March 9–12, 2013; and at the 2013 Annual Meeting of the American Society of Clinical Oncology, Chicago, May 31–June 4, 2013.

The study senior author, Dr Bradley Monk, expect that results change the standard of care for women with advanced cervical cancer. Dr Monk chairs the Gynecologic Oncology Cervical Cancer Committee for the National Cancer Institute funded Gynecologic Oncology Group (GOG).

The first author of the paper is Dr Krishnansu Tewari of the Division of Gynecologic Oncology, University of California, Irvine.

According to Dr Monk, the study results are a significant step forward and the researchers plan adding bevacizumab to a front-line treatment when cancers are more curable, rather than using it at the time of recurrence.

 

Reference

Tewari KS, Sill MS, Long HJ, et al. Improved Survival with Bevacizumab in Advanced Cervical Cancer. N Engl J Med 2014; 370:734-743.