BRAF V600E/V600K Mutations versus Nonstandard Alterations: Prognostic Implications and Therapeutic Outcomes
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 15, 2021
- Source ID
- 10.1158/1535-7163.mct-20-0861
Entities
People
- Donald Barkauskas
- Jose Tinajero
- Mina Nikanjam
- Razelle Kurzrock
Organizations
- American Association for Cancer Research
- National Cancer Institute
- National Institutes of Health
- Ovarian Cancer Research Alliance
- UC San Diego Health System
- United States Department of Defense
- University of California, San Diego
- University of Southern California