Efficacy of encorafenib plus binimetinib in patients with BRAF-mutated melanoma brain metastases: results from the Dutch Melanoma Treatment Registry

Data on the effectiveness of encorafenib/binimetinib in melanoma patients with brain metastases (BMs) are limited. All patients with BRAF V600-mutated melanoma and BMs treated with encorafenib/binimetinib between 2019 and 2022 in the Netherlands were included from the nationwide Dutch Melanoma Treatment Registry. Patients previously treated with other BRAF/MEK inhibitors were excluded. We analyzed objective response rates (ORR), progression-free survival (PFS), and overall survival (OS). Multivariable Cox regression identified factors associated with survival. Subgroup analyses included asymptomatic versus symptomatic BMs and line of treatment (first-line versus later-line). In total, 190 patients were included. Symptomatic BMs were present in 63 % of patients. Encorafenib/binimetinib was the first-line treatment in 64 % of all patients, while 36 % had prior immunotherapy. Overall, the ORR was 69.4 %, median PFS was 5.5 months (95 %CI 4.9-6.2), and median OS 11.9 months (95 %CI 10.0-15.7). Age ≥ 70, ECOG PS ≥ 2, symptomatic BMs, and elevated LDH were significantly associated with worse survival. Patients with prior immunotherapy had a median PFS of 6.9 months (95 %CI 4.3-9.6) and OS of 17.9 months (95 %CI 13.7-31.2), while this was 4.9 months (95 %CI 4.3-5.5) and 10.1 months (95 %CI 8.1-13.0) in treatment-naïve patients. Median PFS and OS in patients with asymptomatic versus symptomatic BMs were 6.1 months (95 %CI 4.9-9.8) and 20.5 (95 %CI 14.0-NA) versus 5.3 months (95 %CI 4.9-6.3) and 10.7 (95 %CI 8.9-13.7), respectively. Encorafenib/binimetinib has clinical activity in real-world melanoma patients with BMs. Their prognosis is determined by the presence of symptomatic BMs, age, ECOG PS, and LDH levels.