Therapeutic implications of B-RAF mutations in colorectal cancer.

Abstract

Colorectal cancers (CRC) with B-RAF mutation carry a particularly poor prognosis. In this context, the value of first-line intensified chemotherapy associated with an anti-VEGF (Vascular endothelial growth factor) to treat metastatic CRC has recently been called into question. In patients with mutated B-RAF, the efficacy of first-line anti-EGFR (Epidermal Growth Factor Receptor) associated with chemotherapy for treatment of metastatic CRC is uncertain while that of anti-VEGF has been shown to be effective. The therapeutic pathways involving inhibition of B-RAF activity, although ineffective as monotherapy, have received marketing authorization when used in association with anti-EGFR for second-line treatment of metastatic CRC. Immunotherapy has provided very encouraging results in a recent phase III study in patients with microsatellite instability, irrespective of their B-RAF status. Finally, new therapies, targeting other RAF proteins and other specific receptors are currently under development. Surgery for liver metastases in patients with the B-RAF mutation should be considered whenever possible, after a complete search for peritoneal carcinomatosis and distant metastases, similarly to workup for patients without the B-RAF mutation.