LBA26 - Final overall survival analysis of the phase III randomized trial of chemotherapy with and without bevacizumab for advanced cervical cancer: A NRG...

Date 28 September 2014
Event ESMO 2014
Session Gynaecological cancers
Topics Anti-Cancer Agents & Biologic Therapy
Cervical Cancer
Presenter Krishnansu Tewari
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors K.S. Tewari1, M.W. Sill2, R.T. Penson3, H. Huang2, L.M. Ramondetta4, L.M. Landrum5, A. Oaknin6, T.J. Reid7, M.M. Leitao8, B.J. Monk9, H.E. Michael10
  • 1Department Of Obstetrics & Gynecology, University of California, Irvine Medical Center, 92868 - Orange/US
  • 2Statistics & Data Center, Roswell Park Cancer Institute, Buffalo/US
  • 3Hematology/oncology, Massachusetts General Hospital, Boston/US
  • 4Gynecologic Oncology, MD Anderson Hospital & Tumor Institute, Houston/US
  • 5Obstetrics & Gynecology, University of Oklahoma, Oklahoma City/US
  • 6Medical Oncology, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 7Obstetrics & Gynecology, University of Cincinnati, Kettering/US
  • 8Surgical Oncology, Memorial Sloan-Kettering Cancer Center, New York/US
  • 9Division Of Gynecologic Oncology, Creighton University School of Medicine at St. Joseph’s Hospital and Medical Center, Phoenix/US
  • 10Surgical Pathology, Indiana University, Indianapolis/US

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.