TY - JOUR
T1 - Efficacy of encorafenib plus binimetinib in patients with BRAF-mutated melanoma brain metastases
T2 - Results from the Dutch Melanoma Treatment Registry
AU - Bloem, M.
AU - Suijkerbuijk, K. P.M.
AU - Aarts, M. J.B.
AU - van den Berkmortel, F. W.P.J.
AU - Blank, C. U.
AU - Blokx, W. A.M.
AU - Boers-Sonderen, M. J.
AU - Boreel, C. D.M.
AU - de Groot, J. W.B.
AU - Haanen, J. B.A.G.
AU - Hospers, G. A.P.
AU - Kapiteijn, E.
AU - van Not, O. J.
AU - Piersma, D.
AU - Rikhof, B.
AU - Stevense-den Boer, A. M.
AU - van der Veldt, A. A.M.
AU - Vreugdenhil, G.
AU - Wouters, M. W.J.M.
AU - van den Eertwegh, A. J.M.
N1 - Publisher Copyright:
© 2025 The Authors
PY - 2025/6/18
Y1 - 2025/6/18
N2 - 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.
AB - 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.
KW - Advanced melanoma
KW - Binimetinib
KW - BRAF/MEK inhibitors
KW - Brain metastases
KW - Encorafenib
U2 - 10.1016/j.ejca.2025.115514
DO - 10.1016/j.ejca.2025.115514
M3 - Article
SN - 0959-8049
VL - 223
JO - European Journal of Cancer
JF - European Journal of Cancer
M1 - 115514
ER -