The oncologist
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Tremendous progress has been made in the clinical landscape of advanced-stage BRAF V600-mutant melanoma treatment over the past 5 years. Targeted therapies that inhibit specific steps of the mitogen-activated protein kinase pathway have been shown to provide significant overall treatment benefit in patients with this difficult-to-treat disease. Combination therapy with BRAF and MEK inhibitors (dabrafenib plus trametinib or vemurafenib plus cobimetinib, respectively) has become standard of care. ⋯ Additionally, the unique safety profile of the chosen regimen may influence patient selection and monitoring. This review discusses the toxicity profiles of these agents, with a focus on the most commonly reported and serious AEs. Here, we offer practical guidance derived from our clinical experience for the optimal management of key drug-related AEs.
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On August 5, 2016, the U. S. Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA injection, Merck Sharp & Dohme Corp., Kenilworth, NJ) for treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. ⋯ Clinically significant immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, adrenal insufficiency, diabetes mellitus, skin toxicity, myositis, and thyroid disorders. The benefit-risk profile of pembrolizumab was considered acceptable in this patient population. As a condition of accelerated approval, Merck is required to conduct a confirmatory trial; this trial, KEYNOTE-040, is ongoing.