Management of BRAF and MEK inhibitor toxicities in patients with metastatic melanoma

Following the discovery that nearly half of all cutaneous melanomas harbour a mutation in the BRAF gene, molecular targeted kinase inhibitors have been developed for the treatment of metastatic melanoma and have dramatically improved outcomes for those patients with BRAF mutant disease, achieving high levels of objective response and prolonging survival. Since 2011, the specific BRAF targeted agents, vemurafenib and dabrafenib, and the MEK inhibitor, trametinib, have been licensed for the treatment of patients with unresectable or metastatic BRAF mutant melanoma. As with other biological targeted agents, these drugs are associated with predictable patterns of adverse events. Proactive toxicity management is important to ensure maximum treatment benefit and avoid unnecessary treatment discontinuation. We review the most common and serious adverse events associated with BRAF targeted agents and suggest management algorithms to guide practitioners in using these drugs effectively in the clinic.