FDA Approves Avastin to Treat Ovarian Cancer

The Food and Drug Administration (FDA) has approved Avastin (bevacizumab) in combination with chemotherapy for patients with platinum-resistant recurrent ovarian cancer, based on a 62 percent improvement in progression-free survival (PFS) experienced by patients treated with the VEGF inhibitor in the phase 3 AURELIA trial.

The approval follows a priority review, which the FDA reserves for therapies that demonstrate a significant improvement over standard options. In the AURELIA study, the median PFS with Avastin was 6.8 compared with 3.4 months with chemotherapy alone. The objective response rate was 28 percent versus 13 percent, and the median overall survival was 16.6 compared with 13.3 months, with Avastin and chemotherapy, respectively.

The approval marks the first new treatment option for women with this type of ovarian cancer in more than 15 years. Risk of the disease worsening was reduced by 62 percent. In the AURELIA study, 361 patients with platinum-resistant ovarian cancer were randomized to receive chemotherapy alone or in combination with Avastin. Patients in the study had received treatment with no more than two prior chemotherapy regimens.

The chemotherapy given with Avastin was Doxil (pegylated liposomal doxorubicin), weekly paclitaxel or topotecan, and selected by the treating physician. If patients progressed on the chemotherapy alone arm, they were allowed to cross over to the Avastin group. In a subset analysis, women who specifically received Avastin plus paclitaxel experienced a median PFS of 9.6 months compared with 3.9 months with paclitaxel alone. In this same population, the median survival was 22.4 months compared with 13.2 months and the response rate was 53 percent and 30 percent, with Avastin and paclitaxel, respectively.

For women treated with topotecan, PFS was significantly extended with Avastin whereas survival was not. Patients treated with the combination experienced a median PFS of 6.2 compared with 2.1 months with single agent topotecan. Survival was 13.8 months compared with 13.3 months, with Avastin and topotecan, respectively. In the pegylated liposomal doxorubicin (PLD) arm, the median PFS was 5.1 months in patients treated with the combination compared with 3.5 months with PLD alone. The median overall survival was 13.7 months with the combination versus 14.1 months with PLD alone.

The addition of Avastin to chemotherapy resulted in an increase of grade 3/4 hypertension and hand-foot syndrome. Gastrointestinal perforation was seen in 2 percent of patients treated with Avastin compared with none treated with chemotherapy alone.

Results from the AURELIA trial add to several prior phase 3 trials that demonstrated Avastin effectively extends PFS for women with ovarian cancer. In the GOG-0218 and ICON7 studies, Avastin extended PFS for women with advanced ovarian cancer that had not been previously treated. In the OCEANS trial, Avastin improved PFS in women with recurrent, platinum-sensitive disease. However, across the multiple large trials, an extension in survival was not demonstrated.

In August, the FDA approved Avastin 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 survival in the phase 3 GOG 240 study. Avastin, 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 kidney cancer.