Sandra Horning, MD
The FDA has approved bevacizumab (Avastin) in combination with chemotherapy for patients with platinum-resistant recurrent ovarian cancer, based on a 62% improvement in progression-free survival (PFS) experienced by patients treated with the VEGF inhibitor in the phase III AURELIA trial.
The approval follows a priority review, which the FDA reserves for therapies that demonstrate a significant improvement over standard options. In AURELIA, the median PFS with bevacizumab was 6.8 versus 3.4 months with chemotherapy alone (HR = 0.38; 95% CI, 0.30-0.49; P
<.0001). The objective response rate (ORR) was 28% versus 13% and the median overall survival (OS) was 16.6 versus 13.3 months (HR=0.89; CI 95%, 0.69-1.14; P
= not significant), with bevacizumab and chemotherapy, respectively.
“Avastin plus chemotherapy is the first new treatment option for women with this difficult-to-treat type of ovarian cancer in more than 15 years,” Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech, said in a statement. “Risk of the disease worsening was reduced by 62% for women who received Avastin plus chemotherapy in the study, and a notable treatment effect was observed with paclitaxel, which may be important when choosing treatment.”
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). Patients in the study had received treatment with no more than 2 prior chemotherapy regimens. The primary endpoint was PFS by RECIST, with secondary endpoints including ORR and OS.
The chemotherapy administered with bevacizumab was pegylated liposomal doxorubicin (Doxil), weekly paclitaxel, or topotecan. The chemotherapy regimen was selected by the treating physician. 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.
In a subset analysis, women who specifically received bevacizumab plus paclitaxel (n = 60) experienced a median PFS of 9.6 months versus 3.9 months with paclitaxel alone (HR = 0.47; 95% CI, 0.31-0.72). In this same population, the median OS was 22.4 versus 13.2 months (HR = 0.64; 95% CI, 0.41-1.01) and the ORR was 53% and 30%, with bevacizumab and paclitaxel, respectively.
For women treated with topotecan, PFS was significantly extended with bevacizumab whereas OS was not. Patients treated with the combination (n = 57) experienced a median PFS of 6.2 versus 2.1 months with single agent topotecan (n = 63; HR = 0.24; 95% CI, 0.15-0.38). The median OS was 13.8 versus 13.3 months, with bevacizumab and topotecan, respectively (HR = 1.12; 95% CI, 0.73-1.73).
In the pegylated liposomal doxorubicin (PLD) arm, the median PFS was 5.1 months in patients treated with the combination (n = 62) compared with 3.5 months with PLD alone (n = 64; HR = 0.47; 95% CI, 0.32-0.71). The median OS was 13.7 months with the combination versus 14.1 months with PLD alone (HR = 0.94; 95% CI, 0.63-1.42).
The addition of bevacizumab to chemotherapy resulted in an increase of grade 3/4 hypertension (6.7% vs 1.1%) and hand-foot syndrome (4.5% vs 1.7%) versus chemotherapy alone. Gastrointestinal perforation was seen in 2% of patients treated with bevacizumab compared with none treated with chemotherapy alone.
Results from the AURELIA trial add to several prior phase III trials that demonstrated bevacizumab effectively extends 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 OS was not demonstrated.
In August, the FDA approved bevacizumab in combination with paclitaxel and cisplatin or topotecan as a treatment for patients with persistent, recurrent, or metastatic cervical cancer, based on the extension of OS in the phase III GOG 240 study. Bevacizumab, which was first approved in 2004, is indicated as a treatment in various settings for patients with metastatic colorectal cancer, metastatic non-squamous non-small cell lung cancer, recurrent glioblastoma, and metastatic renal cell carcinoma.