CHICAGO—Bevacizumab extended survival by a median of 3.7 months in women with relapsed and advanced cervical cancer, the first time a targeted agent has significantly improved overall survival (OS) in gynecologic cancer, results of a phase 3 randomized Gynecologic Oncology Group (GOG) study concluded at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.
The second interim analysis crossed the boundary for efficacy, warranting early release of the data, said Krishnansu Sujata Tewari, MD, of the University of California Irvine Medical Center, Orange, CA.
The GOG 240 study evaluated bevacizumab in 452 women with chemotherapy-naïve recurrent/persistent and metastatic cervical cancer. Between April 2009 and January 2012, patients were randomly assigned to one of four arms: chemotherapy—cisplatin 50 mg/m2 plus paclitaxel 135 or 175 mg/m2 or topotecan 0.75 mg/m2 plus paclitaxel 175 mg/m2—with or without bevacizumab 15 mg/kg. Cycles were repeated every 21 days until disease progression, unacceptable toxicity, or complete response.
“The randomized treatment groups were similar with regard to age, histology, performance status, previous platinum as a radiosensitizer, and recurrence, persistence, or advanced disease,” he noted.
Primary endpoints were to determine if adding bevacizumab to chemotherapy improved OS; if a non-platinum doublet, topotecan plus paclitaxel, improved OS; and the tolerability of the four regimens. Secondary endpoints were to determine the impact of bevacizumab and non-platinum doublet on progression-free survival (PFS) and overall response rate.
“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,” Dr. Tewari said. Median survival was 15 months in the cisplatin/paclitaxel arm and 12.5 months in the topotecan/paclitaxel arm (P=0.880). In January 2013, the bevacizumab-containing regimens were “declared superior” and in March 2013, ASCO made a rare exception to its confidentiality policy and placed the abstract in the public domain.
At a median follow-up of 20.8 months, median OS for the chemotherapy arm (n=225) was 13.3 months compared with 17.0 months for the chemotherapy plus bevacizumab arm (n=227; hazard ratio [HR], 0.71; one-sided P=0.0035); median PFS was 5.9 versus 8.2 months, respectively (HR, 0.67; P=0.0002). Response rate was 36% in the chemotherapy arm and 48% in the chemotherapy plus bevacizumab arm (P=0.00807).
Compared with chemotherapy alone, treatment with chemotherapy plus bevacizumab was associated with more grade 3-4 bleeding, thrombosis/embolism, and gastrointestinal fistula.
Dr. Tewari said that the benefit with bevacizumab was observed even when disease recurrence was in the irradiated pelvis. In addition, improvement in OS was not accompanied by a decrease in health-related quality of life, with patients receiving bevacizumab reporting 1.2 points lower on average in mean Functional Assessment of Cancer Therapy–Cervix Trial Outcome Index (FACT-Cx TOI; P=0.3).
In discussing the trial, Goffried E. Konecny, MD, pointed out that limitations of the study include no cost-benefit analysis was performed; there is no information on treatment withdrawal regarding chemotherapy or bevacizumab; study results may not be applicable to patients with metastatic disease (17%), and it is not known whether adenocarcinomas derive the same benefit as squamous histologies.
This research was supported by the National Cancer Institute.