The FDA approved bevacizumab (Avastin) for the second-line treatment of patients with metastatic colorectal cancer (mCRC) in combination with fluoropyrimidine-based irinotecan or oxaliplatin chemotherapy. The new indication allows for patients receiving bevacizumab plus an irinotecan- or oxaliplatin-containing chemotherapy in the first line to continue receiving bevacizumab in combination with a different irinotecan- or oxaliplatin-containing chemotherapy after disease progression.

“The majority of people diagnosed with metastatic colorectal cancer receive Avastin plus chemotherapy as their initial treatment,” Hal Barron, MD, chief medical officer and head of Global Product Development at Genentech, which manufactures bevacizumab, said in a statement. “These people now have the option to continue with Avastin plus a new chemotherapy after their cancer worsens, which may help them live longer than changing to the new chemotherapy alone.”

The FDA based its approval on data from the phase III, open-label, multicenter, multinational ML18147 study, which were presented at the 2012 ASCO Annual Meeting. In the trial, 820 patients with mCRC were randomized at progression to second-line treatment with chemotherapy plus bevacizumab (2.5 mg/kg intravenously per week) or chemotherapy alone. Depending on the first-line chemotherapy treatment the patient received (fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based), the chemotherapy regimen was switched in the second-line setting.

The primary endpoint of the trial was overall survival (OS) and was measured from the time that patients were randomized to second-line treatment. Secondary endpoints included progression-free survival (PFS), overall response rate, and safety profile.

Median OS with bevacizumab was 11.2 months versus 9.8 months with chemotherapy alone (hazard ratio [HR] = 0.81; P = .0057). Median PFS was 5.7 months in the bevacizumab arm compared with 4.1 months in patients receiving chemotherapy alone (HR = 0.68; P <.0001). There was no significant difference in response rate in the two cohorts.

Adverse events in the trial were similar to those seen in previous bevacizumab trials. Serious side effects include gastrointestinal perforation, surgery and wound healing problems, and severe bleeding.

The VEGF-inhibitor bevacizumab is also approved to treat patients with mCRC in combination with intravenous 5 fluorouracil-based chemotherapy as an initial treatment and in patients whose cancer has worsened after chemotherapy alone. Bevacizumab is not approved for adjuvant treatment of colon cancer.

Bevacizumab is also approved for use in advanced nonsquamous non–small cell lung cancer, metastatic kidney cancer, and glioblastoma.