The U.S. Food and Drug Administration has approved the use of Avastin (bevacizumab, made by Genentech) in combination with fluoropyrimidine-based irinotecan or fluoropyrimidine-oxaliplatin based chemotherapy to treat patients with metastatic colorectal cancer whose disease has progressed after a first-line bevacizumab-containing regimen.
Bevacizumab, a recombinant humanized monoclonal IgG1 antibody that binds to human vascular endothelial growth factor (VEGF), preventing the interaction of VEGF to its receptors on the surface of endothelial cells, became the first angiogenesis inhibitor to receive FDA approval as a first-line treatment (to be used in combination with an intravenous fluorouracil-based chemotherapy) for patients with previously untreated metastatic colorectal cancer in 2004 (OT, 3/25/04).
The new approval is based on results from a randomized, open-label, multinational Phase III study of 820 patients with metastatic colorectal cancer whose disease had progressed during or within three months of discontinuation of Avastin plus standard first-line irinotecan or oxaliplatin-based chemotherapy. Patients received either irinotecan-based therapy or oxaliplatin-based chemotherapy depending on prior treatment (irinotecan-based regimen for patients who received prior treatment with oxaliplatin, and oxaliplatin-based therapy for patients who received prior treatment with irinotecan).
Avastin was continued until disease progression or unacceptable toxicity. The study showed statistically significant improvement in both overall and progression-free survival for patients receiving cross-over chemotherapy plus Avastin versus patients receiving cross-over chemotherapy alone:
* Median overall survival was 11.2 months for patients in the Avastin-receiving arm compared with 9.8 months for patients receiving cross-over chemotherapy alone; and
* Progression-free survival was 5.7 months compared with four months in those arms, respectively.
The side effects profile was consistent with that established in previously approved indications for the drug.
The recommended dose and schedule in patients receiving Avastin in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based chemotherapy after progression on a first-line Avastin containing regimen is 5 mg/kg administered every two weeks or 7.5 mg/kg administered every three weeks as a 60-minute intravenous infusion.