The FDA has approved bevacizumab (Avastin) for use with fluoropyrimidine-irinotecan-based or fluoropyrimidine-oxaliplatin-based chemotherapy in the treatment of patients with metastatic colorectal cancer whose disease has progressed on a first-line regimen containing bevacizumab.

Bevacizumab, a recombinant humanized monoclonal IgG1 antibody, is a vascular endothelial growth factor-specific angiogenesis inhibitor. Among other indications, the agent had already been approved as a first-line or second-line treatment for metastatic colorectal cancer in combination with intravenous 5-fluorouracil-based chemotherapy.

The FDA’s approval of bevacizumab’s newest indication is based on the results of a randomized, open-label, multinational trial. The study involved 820 men and women (median age 63 years) with metastatic colorectal cancer that progressed during, or within 3 months after discontinuation of, first-line bevacizumab-based combination chemotherapy with either of those fluoropyrimidine regimens.

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The patients had been randomly allocated to receive crossover chemotherapy alone (411 participants) or crossover chemotherapy in combination with bevacizumab (409 participants). That is, they received either irinotecan-based or oxaliplatin-based chemotherapy depending on prior treatment: Patients who received prior treatment with irinotecan now underwent oxaliplatin therapy, and those who originally received oxaliplatin now were given irinotecan. The treatment cycles on both arms were repeated every 2 or 3 weeks, depending on the chemotherapy regimen used.

Bevacizumab was administered by intravenous infusion at a dose of 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks, continuing until disease progression or until toxicity became unacceptable.

A statistically significant improvement in overall survival was observed in persons receiving crossover chemotherapy plus bevacizumab (median overall survival 11.2 months) compared with those receiving crossover chemotherapy alone (median overall survival 9.8 months). Progression-free survival was also significantly better for the bevacizumab patients, at 5.7 months compared with 4.0 months.

No new safety signals were observed in this trial; the safety data were consistent with the known safety profile established in previously approved indications.