Aflibercept. Metastatic colorectal cancer: at least as poorly tolerated as bevacizumab.

The Folfiri protocol is often proposed to patients with metastatic colorectal cancer in relapse or treatment failure after the Folfox protocol. The benefit of adding a monoclonal antibody is far from certain. In two trials, addition of bevacizumab, a VEGF inhibitor, to a second-line regimen prolonged survival by about two months, at a cost of many additional serious or even life-threatening adverse effects. Aflibercept (Zaltrap, Sanofi Aventis), another VEGF inhibitor, has been authorised in the European Union as an adjunct to the Folfiri protocol in patients with metastatic colorectal cancer in treatment failure or relapse after a first-line regimen including oxaliplatin (Folfox protocol, for example). Aflibercept has not been compared with bevacizumab in this setting. In a double-blind, randomised, placebo-controlled trial including 1226 patients, adding aflibercept to the Folfiri protocol prolonged median overall survival by about 1.5 months. In this trial, 83% of patients in the aflibercept group experienced at least one serious adverse event, versus 62% of patients in the placebo group. Aflibercept had the typical adverse effect profile of VEGF inhibitors, which includes arterial hypertension, arterial thrombosis, pulmonary embolism, bleeding, fistulae, bowel perforation, leukoencephalopathy, and delayed wound healing. Adding aflibercept also increased the frequency of certain adverse effects of the Folfiri protocol, including diarrhoea, dehydration, mucositis, infections and palmoplantar erythrodysesthesia. The adverse effects of aflibercept were fatal in some patients. In practice, patients with metastatic colorectal cancer in treatment failure or relapse after first-line therapy should not expect too much from the addition of aflibercept or bevacizumab to a second-line protocol.