BRAF Mutations in Advanced Cancers: Clinical Characteristics and Outcomes

摘要: Author(s): El-Osta, Hazem; Falchook, Gerald; Tsimberidou, Apostolia; Hong, David; Naing, Aung; Kim, Kevin; Wen, Sijin; Janku, Filip; Kurzrock, Razelle | Abstract: BackgroundOncogenic BRAF mutations have been found in diverse malignancies and activate RAF/MEK/ERK signaling, a critical pathway of tumorigenesis. We examined the clinical characteristics outcomes patients with mutant (mut) advanced cancer referred to phase 1 clinic.MethodsWe reviewed records 80 consecutive mutBRAF 149 wild-type (wt) (matched by tumor type) Clinical Center for Targeted Therapy analyzed their outcome.ResultsOf cancer, 56 had melanoma, 10 colorectal, 11 papillary thyroid, 2 ovarian esophageal cancer. Mutations codon 600 were 77 (62, V600E; 13, V600K; 1, V600R; unreported). Multivariate analysis showed less soft tissue (Odds ratio (OR) = 0.39, 95%CI: 0.20-0.77, P 0.007), lung (OR 0.38, 0.19-0.73, p 0.004) retroperitoneal metastases 0.34, 0.13-0.86, 0.024) more brain 2.05, 1.02-4.11, 0.043) versus wtBRAF. Comparing corresponding wtBRAF, melanoma insignificant trend longer median survival from diagnosis (131 vs. 78 months, 0.14), while colorectal an shorter (48 53 0.22). In V600K comparison other associated frequent (75% 36.3%, 0.02) (91.6% 47.7%, time metastasis death (19 0.046 322 0.024 respectively). Treatment RAF/MEK targeting agents (Hazard (HR) 0.16, 0.03-0.89, 0.037) any decrease size after referral (HR 0.07, 0.015-0.35, 0.001) correlated patients.ConclusionsBRAF appears be druggable mutation that also defines subgroups phenotypic overlap, albeit differences correlate histology or site mutation.