BRAF targets in melanoma. Biological mechanisms, resistance, and drug discovery. Cancer drug discovery and development. Volume 82. Ed. Ryan J. Sullivan. Springer (2015)
Clinical trials investigating combination BRAF inhibitors and immunotherapeutic strategies to address metastatic melanoma remain in the early stages of patient accrual, and mature response and toxicity data are not yet available. However, some interesting data has emerged regarding toxicity with the combination of BRAF-directed therapy (Vemurafenib) and anti-CTLA-4 (Ipilimumab). Specifically, hepatotoxicity was observed in a phase 1 study of the concurrent administration of these two agents leading to closure of the trial to further accrual. Of note, the grade two or three elevations in liver function tests were completely asymptomatic, and resolved after the therapy was discontinued or with the systemic steroid administration . Nonetheless this highlights the potential for unexpected toxicity in these trials, and suggests the need for well-controlled clinical trials, even when combining FDAapproved agents.
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