According to a cohort study published early online in the Journal of Clinical Oncology, the addition of bevacizumab to cytotoxic combination chemotherapy may be associated with a small improvement in overall survival albeit with an increased risk of stroke and gastrointestinal perforation, but not cardiac events.

Using the Surveillance, Epidemiology, and End Results (SEER) -Medicare linked database, a total of 2,526 patients with stage IV colorectal cancer diagnosed between 2002 and 2007 who received first-line combination chemotherapy with a fluoropyrimidine and either irinotecan (33%) or oxaliplatin (67%) were evaluated. Thirty-six percent of patients also received bevacizumab with first-line therapy. The primary outcome was overall survival, and secondary outcomes were bevacizumab-associated toxicities, including the incidence of stroke, myocardial infarction, and GI perforation.

• In the primary cohort inclusive of patients diagnosed between 2002 and 2007, bevacizumab with combination chemotherapy was associated with improved overall survival (adjusted hazard ratio [HR], 0.85; 95% CI, 0.78 to 0.93) - Median overall survival was 19.0 months with bevacizumab and 15.9 months without bevacizumab
• The observed survival advantage of bevacizumab was more apparent with irinotecan-based chemotherapy (HR, 0.80; 95% CI, 0.66 to 0.97) than with oxaliplatin-based chemotherapy (HR, 0.96; 95% CI, 0.86 to 1.07).
• Combination chemotherapy with bevacizumab, versus combination chemotherapy without bevacizumab, was associated with increased risk of stroke (4.9% vs. 2.5%, respectively; P < 0.01) and GI perforation (2.3% v s. 1.0%, respectively; P < 0.01).
• Cardiac events and venous thrombosis were not increased with bevacizumab.

The study concludes that this analysis suggests that the benefit derived from the use of bevacizumab is more prominent with irinotecan-based regimens, with marginal benefit in oxaliplatin-treated patients, but the authors also advise that “On balance, elderly patients with colorectal cancer can be counselled that including bevacizumab in first-line therapy regimens for metastatic colorectal cancer seems to be no more than marginally effective.”