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BRAF plus MEK inhibitor combinations are currently FDA approved for melanoma, non-small cell lung cancer, and anaplastic thyroid cancer. The lack of clinical benefit with BRAF inhibition in BRAF V600 mutated colorectal cancer has prevented its tissue-agnostic drug development. We reviewed the AACR GENIE database for the prevalence of BRAF V600 mutations across tumor types. We reviewed the literature for case reports of clinical responses, outcomes in patients with BRAF V600 mutation-positive non-melanoma malignancies who received BRAF inhibitor therapy, and data from published adult and pediatric trials. BRAF V600 mutations are prevalent across multiple non-melanoma malignancies (&amp;gt; 40 different tumor types), lead to oncogene addiction, and are clinically actionable in a broad range of adult and pediatric non-melanoma rare malignancies. Continued tissue-agnostic drug development is warranted beyond the current BRAF plus MEK approved cancers.

Tissue-Agnostic Activity of BRAF plus MEK Inhibitor in BRAF V600–Mutant Tumors