TY - JOUR
T1 - Induction therapy with BRAF/MEK inhibitors versus upfront ipilimumab/nivolumab in poor prognostic advanced melanoma
AU - Bloem, M.
AU - van den Eertwegh, A. J.M.
AU - Haanen, J. B.A.G.
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 - Hospers, G. A.P.
AU - Kapiteijn, E.
AU - Piersma, D.
AU - Rikhof, B.
AU - Simkens, L. H.J.
AU - Stevense-den Boer, A. M.
AU - van der Veldt, A. A.M.
AU - Wouters, M. W.J.M.
AU - Suijkerbuijk, K. P.M.
N1 - Publisher Copyright: © 2025 The Authors.
PY - 2025/11/17
Y1 - 2025/11/17
N2 - BRAF/MEK inhibitor induction therapy (BRAF/MEK-i) followed by ipilimumab/nivolumab (IPI/NIVO) did not show benefit over upfront IPI/NIVO in unselected advanced melanoma patients in clinical trial setting. We investigated BRAF/MEK-i in subgroups of patients with advanced melanoma and poor prognostic characteristics. Patients with BRAF-mutant advanced melanoma treated with BRAF/MEK inhibitors (<120 days) followed by planned switch to IPI/NIVO or upfront IPI/NIVO between 2016 and 2023 were included from the nationwide Dutch Melanoma Treatment Registry. Progression-free survival (PFS) and overall survival (OS) were analyzed in propensity score-matched cohorts and subgroups (LDH 250–500 and >500U/L, symptomatic and asymptomatic brain metastases (BMs), liver metastases, ≥ 3 metastatic sites, and ECOG PS ≥ 2). We included 709 patients (187 BRAF/MEK-i and 522 upfront IPI/NIVO). In the matched cohort (n = 280), median PFS and OS were not statistically significantly different: 6.5 (95 %CI 5.3–8.1) and 20.0 (95 %CI 17.2–35.3) months for BRAF/MEK-i vs. 6.6 (95 %CI 4.3–11.3) and 54.0 (95 %CI 21.7–64.4) months for upfront IPI/NIVO. Upfront IPI/NIVO showed significantly improved PFS compared to BRAF/MEK-i for asymptomatic BMs (median 9.4 months (95 %CI 6.3–28.2) vs. 4.8 months (95 %CI 4.1–5.3); p < 0.01), and significantly improved OS for asymptomatic BMs (median 60.4 months (95 %CI 39.1-NR) vs. 16.2 months (95 %CI 11.7–31.8); p < 0.01), liver metastases (median 49.8 months (95 %CI 32.1–60.3) vs. 14.1 months (95 %CI 12.1–20.5); p < 0.01), LDH 250–500 U/L (median 52.7 months (95 %CI 35.1-NR) vs. 20.1 months (95 %CI 13.9–35.5); p = 0.03), and ≥ 3 metastatic sites (median 54.0 months (95 %CI 39.1-NR) vs. 16.7 months (95 %CI 13.8–24.8); p < 0.01). BRAF/MEK-i showed no significant benefit over upfront IPI/NIVO in matched and stratified analyses according to prognostic characteristics.
AB - BRAF/MEK inhibitor induction therapy (BRAF/MEK-i) followed by ipilimumab/nivolumab (IPI/NIVO) did not show benefit over upfront IPI/NIVO in unselected advanced melanoma patients in clinical trial setting. We investigated BRAF/MEK-i in subgroups of patients with advanced melanoma and poor prognostic characteristics. Patients with BRAF-mutant advanced melanoma treated with BRAF/MEK inhibitors (<120 days) followed by planned switch to IPI/NIVO or upfront IPI/NIVO between 2016 and 2023 were included from the nationwide Dutch Melanoma Treatment Registry. Progression-free survival (PFS) and overall survival (OS) were analyzed in propensity score-matched cohorts and subgroups (LDH 250–500 and >500U/L, symptomatic and asymptomatic brain metastases (BMs), liver metastases, ≥ 3 metastatic sites, and ECOG PS ≥ 2). We included 709 patients (187 BRAF/MEK-i and 522 upfront IPI/NIVO). In the matched cohort (n = 280), median PFS and OS were not statistically significantly different: 6.5 (95 %CI 5.3–8.1) and 20.0 (95 %CI 17.2–35.3) months for BRAF/MEK-i vs. 6.6 (95 %CI 4.3–11.3) and 54.0 (95 %CI 21.7–64.4) months for upfront IPI/NIVO. Upfront IPI/NIVO showed significantly improved PFS compared to BRAF/MEK-i for asymptomatic BMs (median 9.4 months (95 %CI 6.3–28.2) vs. 4.8 months (95 %CI 4.1–5.3); p < 0.01), and significantly improved OS for asymptomatic BMs (median 60.4 months (95 %CI 39.1-NR) vs. 16.2 months (95 %CI 11.7–31.8); p < 0.01), liver metastases (median 49.8 months (95 %CI 32.1–60.3) vs. 14.1 months (95 %CI 12.1–20.5); p < 0.01), LDH 250–500 U/L (median 52.7 months (95 %CI 35.1-NR) vs. 20.1 months (95 %CI 13.9–35.5); p = 0.03), and ≥ 3 metastatic sites (median 54.0 months (95 %CI 39.1-NR) vs. 16.7 months (95 %CI 13.8–24.8); p < 0.01). BRAF/MEK-i showed no significant benefit over upfront IPI/NIVO in matched and stratified analyses according to prognostic characteristics.
UR - https://www.scopus.com/pages/publications/105020599149
U2 - 10.1016/j.ejca.2025.116062
DO - 10.1016/j.ejca.2025.116062
M3 - Article
C2 - 41129985
AN - SCOPUS:105020599149
SN - 0959-8049
VL - 230
JO - European Journal of Cancer
JF - European Journal of Cancer
M1 - 116062
ER -
