Multiple studies have examined the relationship between BRAF mutation and overall survival in patients with stage III and stage IV disease.1-6 In a prospective study of 197 metastatic melanoma patients, overall survival was significantly decreased in those with a BRAF mutation who had not received treatment compared with those patients with wild-type BRAF (see figure below).1
Adapted with permission from: Long GV et al. J Clin Oncol. 2011;29(10):1239-46.
In a study of patients with resected stage IIB, IIC, or III melanoma, patients with BRAF mutation–positive disease showed a poorer overall survival than patients with wild-type BRAF (see figure below).7
Adapted from Corrie PG, et al. Ann Oncol. 2018;29(8):1843-52. Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
A meta-analysis of 6 clinical studies of checkpoint inhibitors was conducted to evaluate the survival in different clinical and molecular subgroups based on PD-1 gene expression status, BRAF gene mutation status, serum LDH level, and demographic factors. The 6 studies included CheckMate 037, CheckMate 066, CheckMate 067, CheckMate 069, KEYNOTE-006, and KEYNOTE-002. Looking specifically at the BRAF gene mutation subgroups, a benefit in overall survival was observed in the BRAF wild-type subgroup (HR, 0.65 [95% CI, 0.49-0.85]; P = .002). However, a significant difference was not observed in the BRAF-mutant subgroup (HR, 1.10 [95% CI, 0.74-1.62]; P = .64). This study showed that in patients with BRAF-mutant melanoma, checkpoint inhibitors did not have a significant impact on overall survival.
Recognising the difference in survival in patients with and without BRAF mutation suggests the activating mutation may make a patient more vulnerable to a worse prognosis. Thus, this highlights the importance of identifying BRAF mutations early in the disease to help inform treatment decisions.