Abstract
INTRO/OBJECTIVE
A mutation of the BRAF protein is seen in approximately 50% of melanoma patients. Immune checkpoint inhibitors (ICI) are standard therapy in melanoma patients independent of a patient’s BRAF status. The primary objective of this study is to investigate the impact of BRAF status in patients treated with ICI compared to non-ICI systemic therapy on overall survival (OS) in patients with melanoma brain metastasis (MBM).
METHODS
We reviewed 351 patients with MBM treated at our tertiary care center between 2000 and 2018. Of these, 144 had known BRAF status, 71 of which were BRAF mutant and 73 were BRAF wild-type. OS was calculated from the date of diagnosis of MBM to compare the efficacy of ICI to other systemic therapies. Many of these patients received multiple lines of treatment including targeted therapies at some point during their care. The log-rank test and Cox proportional hazard model was utilized to determine differences in OS.
RESULTS
Eighty-four percent of patients received local therapy that included either surgery, stereotactic radiosurgery, or whole brain radiation therapy. In BRAF wild-type patients, 40 received ICI and 33 underwent non-ICI systemic therapy with a median survival (5.6 vs 7.1 months) and 2-year survival (28% vs 32%), respectively (p=0.64). Of the BRAF mutant patients, 33 received ICI and 38 did not with a median survival (17.1 vs 9.0 months) and 2-year survival (36% and 19%), respectively (p=0.014). When controlling for age, KPS, ECM, and number of lesions, BRAF mutant MBM patients treated with ICI compared to non-ICI had an OS hazard ratio, HR=0.4 (95% CI=0.21 – 0.78, p=0.0069).
CONCLUSION
ICI therapy in BRAF mutant MBM patients results in improved OS compared to those with non-ICI systemic therapy. No such difference was observed in the BRAF wild-type cohort.