FDA Expands Avastin Label

New ovarian cancer indication joins several previous cancer approvals

The FDA has given the nod to bevacizumab (Avastin, Genentech), either in combination with carboplatin and paclitaxel or in combination with carboplatin and gemcitabine chemotherapy, followed by bevacizumab alone, for the treatment of patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

The use of Avastin in combination with chemotherapy for these cancers was granted priority review, and the new approval was based on results from two randomized, controlled phase 3 trials, GOG-0213 and OCEANS. The GOG-0213 study demonstrated that adding bevacizumab to chemotherapy showed an overall survival (OS) difference of five months compared with chemotherapy alone (median OS: 42.6 months vs. 37.3 months, respectively). Both the GOG-0213 and OCEANS studies demonstrated a significant improvement in progression-free survival (PFS). The GOG-0213 study showed that women lived a median of 3.4 months longer without disease progression with the addition of bevacizumab to chemotherapy compared with chemotherapy alone (median PFS: 13.8 months vs. 10.4 months, respectively).

In the OCEANS study, bevacizumab in combination with chemotherapy significantly improved PFS compared with placebo plus chemotherapy (median PFS: 12.4 months vs. 8.4 months, respectively; P < 0.0001). OS, one of the secondary endpoints in the OCEANS study, was not significantly improved with the addition of bevacizumab to chemotherapy.

Bevacizumab is a biologic antibody designed to bind specifically to vascular endothelial growth factor (VEGF) proteins, which play an important role throughout the lifecycle of a tumor in the development and maintenance of angiogenesis. Bevacizumab is designed to interfere with the tumor blood supply by directly binding to the VEGF protein, thereby preventing interactions with receptors on blood-vessel cells. The tumor blood supply is thought to be critical to a tumor's ability to grow and metastasize.

In November 2014, bevacizumab was approved in the United States for the treatment of women with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan chemotherapy.

Current indications for bevacizumab include:

  • First- or second-line treatment of patients with metastatic colorectal cancer in combination with intravenous 5 fluorouracil–based chemotherapy
  • Second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line bevacizumab-containing regimen, in combination with fluoropyrimidine/irinotecan- or fluoropyrimidine/oxaliplatin-based chemotherapy
  • First-line treatment of patients with unresectable, locally advanced, recurrent, or metastatic nonsquamous, non–small-cell lung cancer in combination with carboplatin and paclitaxel chemotherapy
  • Treatment of metastatic renal cell carcinoma in combination with interferon alfa
  • Treatment of persistent, recurrent, or metastatic carcinoma of the cervix in combination with paclitaxel and cisplatin or paclitaxel and topotecan
  • Treatment of platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in women who received no more than two prior chemotherapy treatments, in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan
  • Treatment of patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, in combination with carboplatin and paclitaxel or with carboplatin and gemcitabine, followed by bevacizumab

Source: Genentech; December 6, 2016.