Bevacizumab improves survival in patients with metastatic colorectal cancer when combined with standard chemotherapy, according to a presentation at the annual meeting of the American Society of Clinical Oncology.

The current study is the first major clinical trial to demonstrate a benefit from an agent in the anti-angiogenesis class. Bevacizumab is a monoclonal antibody targeted against vascular endothelial growth factor.

Patients were randomized to irinotecan, 5-fluorouracil, and leucovorin plus bevacizumab (403 patients) or the three-drug chemotherapy regimen plus placebo (412 patients). When progression of disease was noted, patients were removed from the blinded study and patients who had received bevacizumab had the option of continuing the experimental agent in combination with second-line chemotherapy.

The primary clinical endpoint was survival, with secondary endpoints including progression free survival, objective response rate, duration of response, and quality of life.

When the 2 treatment arms were compared, researchers found that people who received the 3-drug regimen plus bevacizumab had a median survival of 20.3 months versus 15.6 months for those who received standard chemotherapy plus placebo. In addition, inclusion of bevacizumab to chemotherapy resulted in a delay in progression of disease of 10.6 months versus 6.2 months and a partial response rate of 45 percent versus 35 percent.

Bevacizumab was better tolerated among the phase III participants than expected. Phase II data had indicated bleeding, thrombosis, proteinuria, and hypertension as possible safety concerns. However, only grade III hypertension was noted at an increased frequency in the phase III study, and it was readily managed with oral medication.

Lead author Herbert Hurwitz, MD, noted “This is the first proof of principle showing that a targeted cancer therapy in general and an angiogenesis inhibitor in particular works against colorectal cancer.”