Sandra Horning, MD
The FDA has assigned a priority review designation to bevacizumab (Avastin) in combination with chemotherapy for patients with recurrent platinum-resistant ovarian cancer. Based on the time of submission, Genentech, the company that markets the drug, announced an FDA action date of November 19, 2014.
The priority review was based on results from the phase III AURELIA trial, which demonstrated that bevacizumab with chemotherapy reduced the risk of disease progression by 52% compared with chemotherapy alone for patients with platinum-resistant ovarian cancer. Results from the study were initially presented at the 2012 ASCO Annual Meeting and were subsequently published in the Journal of Clinical Oncology
in March 2014.
The AURELIA trial adds to results from several prior phase III trials that demonstrated bevacizumab effectively extends progression-free survival (PFS) for women with ovarian cancer. In the GOG-0218 and ICON7 studies, frontline bevacizumab extended PFS for women with advanced ovarian cancer. In the OCEANS trial, bevacizumab improved PFS in women with recurrent, platinum-sensitive disease. However, across the multiple large trials, an extension in overall survival (OS) was not demonstrated, hampering prior regulatory submissions.
“The majority of women with ovarian cancer will become resistant to platinum therapy and a quarter of women will have platinum-resistant disease at the time of a first recurrence. New treatment options are needed,” Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech, said in a release. “We look forward to working with the FDA to bring this potential option to women with this difficult-to-treat cancer as soon as possible.”
In the AURELIA study, 361 patients with platinum-resistant ovarian cancer were randomized 1:1 to receive chemotherapy alone (n = 182) or in combination with bevacizumab (n = 179). The primary endpoint was PFS by RECIST, with secondary endpoints including objective response rate (ORR) and OS.
Chemotherapy was selected by the treating physician and consisted of pegylated liposomal doxorubicin (Doxil), weekly paclitaxel, or topotecan. Bevacizumab was administered at 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks. Crossover to the bevacizumab arm was allowed following progression on chemotherapy.
The median PFS with bevacizumab was 6.7 versus 3.4 months with chemotherapy alone (HR = 0.48; 95% CI, 0.38-0.60; P
<.001). A statistically significant extension in OS was not demonstrated in the total population. The median OS was 16.6 months with bevacizumab versus 13.3 months with chemotherapy alone (HR=0.85; P
<.174). The ORR was 27.3% versus 11.8%, for bevacizumab and chemotherapy, respectively (P
In a subset analysis, women who specifically received bevacizumab plus paclitaxel (n = 60) experienced a median PFS of 10.4 months versus 3.9 months with paclitaxel alone (HR=0.46). In this same population, the median OS was 22.4 versus 13.2 months, for bevacizumab and paclitaxel, respectively (HR=0.65; 95% CI, 0.42-1.02).
The addition of bevacizumab to chemotherapy resulted in an increase of grade ≥2 hypertension (20% vs 7%) and proteinuria (11% vs 1%) versus chemotherapy alone. Gastrointestinal perforation was seen in 2% of patients treated with bevacizumab compared with none treated with chemotherapy alone.
Bevacizumab is approved in various settings for patients with metastatic colorectal cancer, metastatic non-squamous non-small cell lung cancer, recurrent glioblastoma, and metastatic renal cell carcinoma.
The FDA priority review designation is reserved for therapies that demonstrate a significant improvement over standard options. At this point, few therapeutic options are available for patients with platinum-resistant ovarian cancer, marking an unmet need.