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@ARTICLE{Lodde:301766,
author = {G. C. Lodde and J. C. Hassel and I. von Wasielewski and F.
Meier and P. Mohr and K. Kähler and A. Hauschild and V.
Glutsch and H. Stege and C. Berking and S. Hüning and J.
Huynh and R. Gutzmer and L. Reinhardt and B. Schilling and
C. Loquai and M. Erdmann and A. Stang and B. Kowall and W.
Galetzka and A. Roesch and D. Tilkorn and S. Ugurel and L.
Zimmer and D. Schadendorf$^*$ and A. Forschner and E.
Livingstone},
title = {{L}ong-term follow-up of real-world adjuvant anti-{PD}1
checkpoint inhibition and targeted therapy in stage {III}
melanoma patients.},
journal = {Journal of clinical oncology},
volume = {43},
number = {25},
issn = {0732-183X},
address = {Alexandria, Va.},
publisher = {American Society of Clinical Oncology},
reportid = {DKFZ-2025-01146},
pages = {2793-2805},
year = {2025},
note = {2025 Sep;43(25):2793-2805},
abstract = {Adjuvant treatment with immune checkpoint inhibition (PD1)
and targeted therapy (TT) with BRAF+MEK inhibitors
significantly improved recurrence-free survival (RFS) of
stage III melanoma patients. We investigated efficacy of
adjuvant therapy with PD1 or TT under real-world
conditions.A total of 589 stage III melanoma patients who
started adjuvant PD1 or TT between June 2018 and September
2019 from 11 major German Dermatologic Cooperative Oncology
Group (DeCOG) skin cancer centers were followed for 4 years.
Endpoints were RFS, overall (OS) and melanoma-specific
survival (MSS). Survival analyses and adjusted hazard ratios
(HRs) were estimated with Kaplan-Meier and Cox proportional
hazards model, inverse probability treatment weighting and
propensity score matching.RFS at 48 months was $42.9\%$
$(95\%$ CI 38.5-47.8) for all PD1 patients and $52.6\%$
$(95\%$ CI 43.6-63.3) for TT patients. Among BRAF-mutated
patients, rate of recurrence was higher for PD1 compared to
TT (HR 1.57, $95\%$ CI 1.09-2.26). OS at 4 years was
$80.8\%$ $[95\%CI$ 73.6-88.7] for BRAF-mutated PD1 patients
and $87.3\%$ $[95\%CI$ 81.0-94.0]) for TT patients. Patients
starting adjuvant PD1 after resection of macroscopic lymph
node metastases had a higher risk of rapid recurrence
(1-year RFS all PD1 $58\%)$ compared to $87\%$ in TT
patients. Rate of recurrence after premature discontinuation
(≤6 vs. >6 months treatment) was higher in TT patients (HR
1.47, $95\%$ CI 0.67-3.23), but not in PD1 patients (HR
1.07, $95\%$ CI 0.73-1.55).BRAF-mutated PD1 patients had a
markedly higher rate of relapse compared to TT patients.
Rapid recurrences occured particulary in PD1-treated
patients with prior macroscopic lymph node metastasis.
Treatment duration shorter than 6 months did not negatively
impact RFS in PD1, but in TT patients.},
cin = {ED01},
ddc = {610},
cid = {I:(DE-He78)ED01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40460331},
doi = {10.1200/JCO-24-02776},
url = {https://inrepo02.dkfz.de/record/301766},
}