FDA Grants Priority Review to Bevacizumab (Avastin) for Ovarian Cancer
Approval decision expected in November
The FDA has accepted a supplemental biologics license application (sBLA) for bevacizumab (Avastin, Genentech) plus chemotherapy for the treatment of women with recurrent platinum-resistant ovarian cancer, and has granted the therapy priority review.
The designation of a “priority review” status is given to medications that the FDA believes have the potential to provide “significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.”
The sBLA for bevacizumab plus chemotherapy for recurrent platinum-resistant ovarian cancer was based on data from the phase III AURELIA trial, with an FDA action date of November 19, 2014.
The AURELIA study was a randomized, open-label trial in 361 women with platinum-resistant recurrent epithelial ovarian primary peritoneal or fallopian tube cancer who had received no more than two anticancer regimens prior to enrollment in the trial. The participants were randomly assigned to one of six treatment arms (paclitaxel, topotecan, or liposomal doxorubicin with or without bevacizumab).
The study met its primary endpoint and showed that bevacizumab plus chemotherapy reduced the risk of disease worsening by 52% compared with chemotherapy alone (median progression-free survival [PFS]: 6.7 months vs. 3.4 months, respectively; hazard ratio [HR], 0.48; P < 0.001). No statistically significant difference was seen in the secondary endpoint of overall survival (median OS: 16.6 months vs. 13.3 months; HR, 0.85; P < 0.174).
Women treated with bevacizumab plus paclitaxel (n = 60) experienced a 54% reduction in the risk of their disease worsening compared with those given chemotherapy alone (median PFS: 10.4 months vs. 3.9 months, respectively; HR, 0.46) and a 35% reduction in the risk of death (median OS: 22.4 months vs. 13.2 months; HR, 0.65).
The study showed that women who received bevacizumab plus chemotherapy had a significantly higher rate of tumor shrinkage (objective response rate) compared with chemotherapy alone when evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) criteria (27.3% vs. 11.8%, respectively; P = 0.001).
Grades 3 to 5 adverse events occurring at a higher incidence (greater than 2%) in women receiving bevacizumab plus chemotherapy compared with women receiving chemotherapy alone were hypertension (7% vs. 1%, respectively), proteinuria (2% vs. 0%), and gastrointestinal perforations (2% vs. 0%).
Bevacizumab is a biologic antibody designed to specifically bind to the vascular endothelial growth factor (VEGF) protein, which plays an important role throughout the life cycle of tumors to promote angiogenesis. Bevacizumab is designed to interfere with the tumor’s blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumor’s blood supply is thought to be critical to its ability to grow and metastasize.
Avastin (bevacizumab) is approved for first- and second-line treatment of metastatic colorectal cancer in combination with intravenous 5-fluorouracil (5-FU)-based chemotherapy. Avastin, in combination with fluropyrimidine/irinotecan- or fluoropyrimidine/oxaliplatin-based chemotherapy, is indicated for the second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line bevacizumab-containing regimen. Avastin is not indicated for adjuvant treatment of colon cancer.
Avastin is also approved for first-line treatment of unresectable, locally advanced, recurrent or metastatic, non-squamous, non–small-cell lung cancer in combination with carboplatin and paclitaxel, and for first-line treatment of metastatic renal-cell carcinoma in combination with interferon alfa.
Source: Genentech; July 21, 2014.