ON JUNE 13, 2018, the U.S. Food and Drug Administration (FDA) approved bevacizumab (Avastin) for the treatment of patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer in combination with carboplatin and paclitaxel, followed by single-agent bevacizumab, for stage III or IV disease after initial surgical resection.
Approval was based on Gynecologic Oncology Group (GOG)- 0218 (ClinicalTrials.gov identifier NCT00262847), a multicenter, randomized, double-blind, placebo-controlled, three-arm study evaluating the addition of bevacizumab to carboplatin and paclitaxel for patients with stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer following initial surgical resection. Patients (n = 1,873) were randomized (1:1:1) to receive carboplatin plus paclitaxel without bevacizumab, carboplatin plus paclitaxel with bevacizumab for up to 6 cycles, or carboplatin plus paclitaxel with bevacizumab for 6 cycles followed by single-agent bevacizumab for up to 16 additional doses. Bevacizumab was administered at 15 mg/kg intravenously every 3 weeks.
Key Findings
THE PRIMARY efficacy outcome was investigator-assessed progression-free survival. The estimated median progression-free survival was 18.2 months for patients receiving bevacizumab with chemotherapy followed by single-agent bevacizumab (hazard ratio [HR] = 0.62, 95% confidence interval [CI] = 0.52–0.75; P < .0001). For those receiving bevacizumab with chemotherapy without single-agent bevacizumab, the estimated median progression-free survival was 12.8 months (HR = 0.83, 95% CI = 0.70– 0.98; not significant). For patients receiving chemotherapy without bevacizumab, the estimated median progression-free survival was 12.0 months. Estimated median overall survival was 43.8 months in the arm receiving bevacizumab with chemotherapy followed by bevacizumab compared to 40.6 months in the chemotherapy-alone arm (HR = 0.89, 95% CI = 0.76–1.05).
Adverse events occurring at higher incidence (≥ 5%) of patients receiving bevacizumab in GOG-0218 were diarrhea, nausea, stomatitis, fatigue, arthralgia, muscular weakness, pain in the extremities, dysarthria, headache, dyspnea, epistaxis, nasal mucosal disorder, and hypertension. ■
