Bevacizumab with Chemotherapy Approved by FDA for Ovarian Cancer

Officials with the FDA have approved bevacizumab (Avastin, Genentech) in combination with carboplatin and paclitaxel for patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer, followed by single-agent bevacizumab, for stage III or IV disease after initial surgical resection.

The recommended bevacizumab dose is 15 mg/kg every 3 weeks with carboplatin and paclitaxel for up to 6 cycles, followed by 15 mg/kg every 3 weeks as a single- agent, for a total of up to 22 cycles.

Bevacizumab was approved as an orphan product based on GOG-0218, a multicenter, randomized, double-blind, placebo-controlled, 3-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. Adverse effects experienced by at least 5% of patients receiving bevacizumab were diarrhea, nausea, stomatitis, fatigue, arthralgia, muscular weakness, pain in extremity, dysarthria, headache, dyspnea, epistaxis, nasal mucosal disorder, and hypertension. Grade 3-4 adverse effects occurring ≥2% of patients in either of the bevacizumab arms versus the control arm were fatigue, hypertension, platelet count decreased, and white blood cell count decreased.

In the trial, patients (n=1,873) were randomized (1:1:1) to 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. Throughout the trial, 1,215 patients received at least one bevacizumab dose.

The primary efficacy outcome was investigator-assessed progression-free survival (PFS); and overall survival (OS) was a secondary outcome. The estimated median PFS was 18.2 months for patients receiving bevacizumab with chemotherapy followed by single-agent bevacizumab (HR 0.62; 95% CI: 0.52, 0.75; p<0.0001). For those receiving bevacizumab with chemotherapy without single-agent bevacizumab, the estimated median PFS was 12.8 months (HR 0.83; 95% CI: 0.70, 0.98; not significant). For patients receiving chemotherapy without bevacizumab, the estimated median PFS was 12.0 months. Estimated median OS was 43.8 months in the 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).

Reference

U.S. Food and Drug Administration. FDA approves bevacizumab in combination with chemotherapy for ovarian cancer [news release]. Spring Hill, MD: June 13, 2018; FDA website. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm610664.htm?utm_campaign=Oncology%206%2F13%2F2018&utm_medium=email&utm_source=Eloqua&elqTrackId=aedf1123feb446ac8126d28a2d6ce8d7&elq=5f047105eef5491fbc61687ac5a9000d&elqaid=3898&elqat=1&elqCampaignId=3025. Accessed June 13, 2018.