Combination Therapies Building on the Efficacy of CTLA4 and BRAF Inhibitors for Metastatic Melanoma

The demonstration of improved survival with the anti-CTLA4 antibody ipilimumab and the BRAF inhibitor vemurafenib in patients with metastatic melanoma is arguably the most significant advance in the treatment for these patients in the last 30 years. However, the majority of patients will either not experience response, or will experience response and then progression, when receiving these therapies, so additional treatment options are required. Since these agents have been developed with a refined understanding of their mechanism of action and mechanisms leading to resistance are being elucidated, then combination therapies building on these single-agent therapies can be designed rationally. Such combinations are being tested both preclinically and in the clinic, and provide a strong promise to improve on the current treatment approaches for patients with metastatic melanoma.