Hepatotoxicity with Combination of Vemurafenib and Ipilimumab

Abstract

There has been great interest in testing combination therapy with the BRAF inhibitor vemurafenib and the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4)–blocking antibody ipilimumab, currently the only two agents approved for the treatment of advanced melanoma on the basis of improved overall survival.¹ Vemurafenib and ipilimumab have different mechanisms of action, and preclinical studies have suggested that BRAF inhibitors may enhance immune-cell function and antigen presentation.^2-5 The only clinically significant overlapping toxic effects for these agents are in skin and liver, which rarely limit their use in patients. Therefore, ample rationale exists to investigate combined therapy with these two agents.