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@ARTICLE{KropfSanchen:302860,
author = {C. Kropf-Sanchen$^*$ and A. Rasokat and P. Christopoulos
and C. Wenzel and T. Wehler and M. Rost and J. Kulhavy and
N. Reinmuth and C. Schulz and M. Scheffler and J. Wolf and
R. Büttner and S. Merkelbach-Bruse and M. Thomas and A.
Stenzinger and M. Schütz and A. Bräuninger and M. Demes
and H.-D. Hummel and N. Pfarr and N. T. Gaisa and J. Rawluk
and E. Berezucki and K. T. Lutz and S. Galda and H. Jacobi
and M. Collienne$^*$ and M. Janning$^*$ and T. Brummer$^*$
and S. Loges$^*$},
collaboration = {n. L. Cancer},
title = {{T}reatment outcome of {NSCLC} patients with
{BRAF}non-{V}600{E} mutations: a retrospective, multicentre
analysis within the national {N}etwork {G}enomic {M}edicine
(n{NGM}) {L}ung {C}ancer in {G}ermany.},
journal = {ESMO open},
volume = {10},
number = {8},
issn = {2059-7029},
address = {[London]},
publisher = {Elsevier},
reportid = {DKFZ-2025-01400},
pages = {105124},
year = {2025},
note = {#EA:A420#LA:A420#},
abstract = {Non-small-cell lung cancer patients with BRAFV600E
mutations benefit from targeted and (chemo-)immune therapy.
However, treatment of BRAFnon-V600E mutations poses
substantial challenges due to biological heterogeneity,
different clinicogenomic features and limited therapy
outcome data.We conducted a retrospective analysis of
BRAFnon-V600E mutation patients in the national Network
Genomic Medicine Lung Cancer, assessing treatment outcomes
upon targeted and (chemo-)immune therapy. Additionally, we
evaluated mitogen-activated protein kinase
(MEK)/extracellular-signal-regulated kinase (ERK) activation
potential of selected, previously not characterized
mutations in vitro.Fifty-three patients with 11 different
BRAFnon-V600E mutations undergoing targeted and/or
(chemo-)immune therapy were identified. Patients with class
I mutations achieved the longest progression-free survival
(PFS) under targeted therapy [median PFS (mPFS) 9.8 months],
whereas chemotherapy and chemoimmunotherapy led to an mPFS
of 35 and 27 months, respectively. In patients with class II
mutations, targeted therapy led to an mPFS of 6.3 months
while chemotherapy, chemoimmunotherapy and immunotherapy
resulted in an mPFS of 3.5, 3.7 and 3.6 months,
respectively. Preclinical characterization demonstrated MEK
phosphorylation potential and hence actionability of BRAF
class II mutations G469A, G469R, G469V and BRAF K601.
Patients exhibiting class III mutations did not respond to
targeted therapy (mPFS 2.6 months), but showed responses to
chemotherapy (mPFS 4.2 months), chemoimmunotherapy (mPFS
10.9 months) and immunotherapy (mPFS 7 months).Patients with
activating BRAFnon-V600E mutations respond to BRAF/MEK
inhibitor or (chemo-)immunotherapy, while those with
non-activating mutations do not benefit from targeted
therapy, but may benefit from (chemo-)immune therapy.
Correlating preclinical activation assays with clinical
outcomes can guide treatment decisions for patients with
BRAFnon-V600E mutations, facilitating personalized treatment
approaches.},
keywords = {BRAF(non-V600E) (Other) / MEK/ERK activation potential
(Other) / non-small-cell lung cancer (Other) / targeted
therapy (Other)},
cin = {A420 / FR01},
ddc = {610},
cid = {I:(DE-He78)A420-20160331 / I:(DE-He78)FR01-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40664146},
doi = {10.1016/j.esmoop.2025.105124},
url = {https://inrepo02.dkfz.de/record/302860},
}