Abstract
ABSTRACT Aim: On August 14, 2014, the United States Food and Drug Administration approved bevacizumab for women with advanced cervical cancer. This regulatory milestone was due to GOG protocol 240 having met its primary endpoint with the arms administering chemotherapy plus bevacizumab resulting in significantly improved overall survival (OS) compared to chemotherapy alone. These results were publically announced following a data freeze on Dec 12, 2012 when 271 deaths had occurred. We now report the planned final analysis of OS. Methods: Phase III randomized clinical trial using a 2x2 factorial design to determine whether chemotherapy plus bevacizumab and/or the non-platinum chemotherapy doublet (topotecan plus paclitaxel) improves OS in women with recurrent/persistent and metastatic cervical cancer. The primary endpoints were OS and toxicity with secondary endpoints being PFS and response. We calculated that we would need to enroll approximately 450 patients with approximately 346 deaths expected to provide the study with 90% power to detect a reduction in the risk of death of at least 30% with either experimental treatment, with the one-sided type I error rate limited to 2.5% for each regimen. Results: The median age was 49 yrs and groups were well-balanced for disease status (70-73% recurrent), prior chemoradiation (74-75%), and in-field pelvic recurrence (53-54%). Gastrointestinal (GI) perforations were reported in 3.2% of patients receiving bevacizumab, all of whom had prior radiotherapy. GI-vaginal fistula occurred in 8.2% of patients treated with bevacizumab vs. 0.9% of those treated with chemotherapy alone. Grade 3+ venous thromboembolic events were reported in 10.6% (chemotherapy plus bevacizumab) vs 5.4% (chemotherapy alone). On March 7, 2014, 348 deaths had occurred and the regimens administering bevacizumab continued to demonstrate a significant improvement in OS over chemotherapy alone: 16.8 mos vs 13.3 mos; HR 0.765 (95% CI: 0.62, 0.95; p = 0.0068). Conclusions: The benefit conferred by the incorporation of bevacizumab is sustained beyond 50 months as evidenced by the survival curves remaining separated. Bevacizumab is the first targeted agent to be granted regulatory approval in the U.S. for treatment of a gynecologic cancer. Disclosure: K.S. Tewari: Contracted research: Endocyte, Amgen, Genentech Speaker's Bureau: Vermillion Advisory Board: Genentech, Caris Extramural funding: National Cancer Institute, Intuitive Surgical Inc.; R.T. Penson: Advisory Board: Genentech; A. Oaknin: Advisory Board: Roche; B.J. Monk: Advisory Board: Genentech/Roche. All other authors have declared no conflicts of interest.
Published Version
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