Efficacy of encorafenib plus binimetinib in patients with BRAF-mutated melanoma brain metastases: results from the Dutch Melanoma Treatment Registry
Menée aux Pays-Bas dans un contexte de vie réelle à partir de données portant sur 190 patients atteints d'un mélanome avec métastases cérébrales, cette étude évalue l'efficacité, du point de vue du taux de réponse objective, de la survie sans progression et de la survie globale, et la toxicité d'un traitement combinant encorafénib et binimétinib
Aim: Data on the effectiveness of encorafenib/binimetinib in melanoma patients with brain metastases (BMs) are limited.
Methods: 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).
Results: 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.
Conclusions: 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.
European Journal of Cancer , résumé, 2025