116712-132

Incorporation of bevacizumab in the treatment of recurrent and metastatic cervical cancer: A phase III randomized trial of the Gynecologic Oncology Group.

Subcategory: 
Category: 
Gynecologic Cancer
Session Type and Session Title: 
Plenary Session, Plenary Session Including FDA Commissioner Address, Public Service Award, and Science of Oncology Award and Lecture
Abstract Number: 

03

Citation: 

J Clin Oncol 31, 2013 (suppl; abstr 3)

Author(s): 

Krishnansu Sujata Tewari, Michael Sill, Harry J. Long, Lois M. Ramondetta, Lisa Michelle Landrum, Ana Oaknin, Thomas J Reid, Mario M. Leitao, Helen E Michael, Bradley J. Monk; University of California, Irvine, Medical Center, Orange, CA; Gynecologic Oncology Group Statistical and Data Center, Buffalo, NY; Mayo Clinic, Rochester, MN; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Oklahoma Health Sciences Center, Oklahoma City, OK; Vall d'Hebron University Hospital, Barcelona, Spain; University of Cincinnati, Cincinnati, OH; Memorial Sloan-Kettering Cancer Center, New York, NY; Clarian North Medical Center, Carmel, IN; Creighton University School of Medicine at St. Joseph's Hospital and Medical Center, Phoenix, AZ


Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures

Abstract: 

Background: Vascular endothelial growth factor (VEGF) promotes angiogenesis, a mediator of disease progression in cervical cancer. Bevacizumab (B), a humanized anti-VEGF monoclonal antibody, has shown single-agent activity in pretreated recurrent disease. We aimed to evaluate B in chemotherapy (CTX)-naive recurrent/persistent/metastatic cervical cancer. Methods: Using a 2x2 factorial design, patients were randomly assigned to CTX with or without B 15 mg/kg. The CTX regimens included cisplatin 50 mg/m2 plus paclitaxel 135-175 mg/m2 and topotecan 0.75 mg/m2 d1-3 plus paclitaxel 175 mg/m2d1. Cycles were repeated every 21 days until disease progression, unacceptable toxicity, or complete response. Overall survival (OS) was the primary endpoint with a reduction in the hazard of death by 30% using anti-VEGF therapy considered important (90% power, 1-sided alpha=2.5%). Final analysis was planned when 346 deaths were observed. Results: 452 patients were accrued from 4/6/09 to 1/3/12. The scheduled interim analysis occurred after 174 patients had died and showed that the topotecan-paclitaxel backbone was not superior to the cisplatin-paclitaxel backbone. A second interim analysis was conducted after 271 deaths. A total of 225 patients received CTX alone and 227 patients received CTX plus B. The randomized treatment groups were similar with regard to age, histology, performance status, previous platinum as a radiosensitizer, and recurrence, persistence, or advanced disease. The B-to-no-B hazard ratio (HR) of death was 0.71 (97.6% CI 0.54-0.95; 1-sided p=0.0035). Median survival was 17 m (CTX plus B) and 13.3 m (CTX alone). The RR were 48% (CTX plus B) and 36% (CTX alone) (p=0.0078). Treatment with B was associated with more grade 3-4 bleeding (5 vs 1%) thrombosis/embolism (9 vs 2%), and GI fistula (3 vs 0%). Conclusions: For the first time a targeted agent significantly improved OS in gynecologic cancer. The second interim analysis crossed the boundary for efficacy, warranting early release of this information. The nearly 4-month increase in median OS with the addition of B to CTX in women with recurrent cervical cancer is considered to be clinically significant. Clinical trial information: NCT00803062.