BRAF V600E/V600K Mutations versus Nonstandard Alterations: Prognostic Implications and Therapeutic Outcomes. Mol Cancer Ther 2021 Jun;20(6):1072-1079
Date
03/17/2021Pubmed ID
33722853Pubmed Central ID
PMC9264327DOI
10.1158/1535-7163.MCT-20-0861Scopus ID
2-s2.0-85107007438 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
BRAF and MEK inhibitors are standard of care for BRAF V600E/K-mutated melanoma, but the benefit of BRAF and/or MEK inhibitors for nonstandard BRAF alterations for melanoma and other cancers is unclear. Patients with diverse malignancies whose cancers had undergone next-generation sequencing were screened for BRAF alterations. Demographics, treatment with BRAF and/or MEK inhibitors, clinical response, progression-free survival (PFS), and overall survival (OS) were determined from review of the electronic medical records for patients with standard BRAF V600E/K versus nonstandard BRAF alterations. A total of 213 patients with BRAF alterations (87 with nonstandard alterations) were identified; OS from diagnosis was significantly worse with nonstandard BRAF versus standard alterations, regardless of therapy [HR (95% confidence interval), 0.58 (0.38-0.88); P = 0.01]. Overall, 45 patients received BRAF/MEK-directed therapy (eight with nonstandard alterations); there were no significant differences in clinical benefit rate [stable disease ≥6 months/partial/complete response (74% vs. 63%; P = 0.39) or PFS (P = 0.24; BRAF V600E/K vs. others)]. In conclusion, patients with nonstandard versus standard BRAF alterations (BRAF V600E/K) have a worse prognosis with shorter survival from diagnosis. Even so, 63% of patients with nonstandard BRAF alterations achieved clinical benefit with BRAF/MEK inhibitors. Larger prospective studies are warranted to better understand the prognostic versus predictive implication of standard versus nonstandard BRAF alterations.
Author List
Nikanjam M, Tinajero J, Barkauskas DA, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
FemaleHumans
Male
Middle Aged
Mitogen-Activated Protein Kinase Kinases
Mutation
Neoplasms
Prognosis
Protein Kinase Inhibitors
Proto-Oncogene Proteins B-raf
Survival Rate
Treatment Outcome