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@ARTICLE{Menzer:304097,
author = {C. Menzer and S. Dugas-Breit and M. Dugas and C. U. Blank
and E. J. Groen and I. Reijers and M. Schlaak and J. Eckardt
and K. P. M. Suijkerbuijk and L. Zimmer$^*$ and D. B.
Johnson and C. Franklin and F. Meiss and B. Schilling and F.
Meier and R. Gutzmer and K.-M. Thoms and T. Haalck and M.
Müller$^*$ and A. Kopp-Schneider$^*$ and M. S. Carlino and
G. V. Long and A. M. Menzies and A. A. M. van der Veldt and
J. W. B. de Groot and T. Eigentler and M. Stevense-den Boer
and C. Pföhler and K. Herbschleb and J. C. Hassel},
title = {{T}argeted therapy for rare {BRAF}-mutated melanoma:
{U}pdated multicenter analysis and launch of a publicly
accessible online outcome database.},
journal = {European journal of cancer},
volume = {228},
issn = {0959-8049},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2025-01765},
pages = {115703},
year = {2025},
abstract = {While BRAF-/MEK-inhibitor therapy is well established in
V600E/K-mutated melanoma, the efficacy in advanced melanoma
with rare BRAF mutations remains uncertain. This is an
updated analysis of an international data collection
including 49 new patients, accompanied by development of a
publicly accessible global database.A retrospective analysis
was conducted at 20 international cancer centers, evaluating
143 patients with rare BRAF V600 (V600-nonE/K; 48 $\%)$ and
non-V600 (52 $\%)$ mutations. Treatments included BRAF/MEK
inhibitor combination therapy (BRAFi/MEKi) and the
respective monotherapies. Clinical outcomes concerning
overall response rate (ORR), progression-free (PFS), and
overall survival (OS) were collected.Included patients had a
median age of 65 years (range 20-93), 101 (71 $\%)$ were
male. Most patients (n = 92, 64 $\%)$ received BRAFi/MEKi,
42 (29 $\%)$ BRAFi monotherapy, and 9 (6 $\%)$ MEKi
monotherapy. The ORR was 35 $\%$ and higher in V600-nonE/K
(45 $\%)$ than non-V600 melanomas (26 $\%,$ p = 0.025).
Median duration of response was similar, with 8.2 months
(range 2.9-53.1 +) for V600-nonE/K and 7.4 months (range
0.8-73.8 +) for non-V600. Combination therapy achieved best
results in both groups, however, differences between
V600-nonE/K and non-V600mutation were only found in ORR (51
$\%$ vs. 33 $\%,$ p = 0,11) and median PFS (6.5 vs. 3.2
months, p = 0.01). Patients with the longest PFS (> 50
months) had V600D/R, $V600_K601D/E/N$ or K601E/N-,
L597V/S/R/Q/P/K- mutations. OS was similar in both groups
(16.1 vs. 11.7 months, p = 0.96). Of note, in non-V600
melanomas MEKi monotherapy revealed similar response rates
as combination treatment (ORR 33 $\%,$ PFS 3 months);
however, median OS was shorter (6.6 months, p = 0.02).This
updated analysis reinforces the benefit of BRAFi/MEKi
therapy in rare BRAF mutations. A database for ongoing data
collection was developed and is available at
https://www.klinikum.uni-heidelberg.de/en/hautklinik-zentrum/hauttumorzentrum/forschung/datenbank-seltene-braf-mutationen.},
keywords = {BRAFi (Other) / MEKi (Other) / Melanoma (Other) / Non-V600
(Other) / Rare BRAF mutation (Other) / Targeted therapy
(Other) / V600 (Other)},
cin = {ED01 / C060},
ddc = {610},
cid = {I:(DE-He78)ED01-20160331 / I:(DE-He78)C060-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40850313},
doi = {10.1016/j.ejca.2025.115703},
url = {https://inrepo02.dkfz.de/record/304097},
}