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@ARTICLE{Regan:304582,
author = {M. M. Regan and P. A. Ascierto and E. J. Lipson and J.
Palaia and A. Moshyk and A. Selvan and C. D. Lao and M. B.
Atkins and D. F. McDermott and R. Potluri and S. Ranjan and
S. Bilthare and G. V. Long and F. Stephen Hodi and H. Tawbi
and D. Schadendorf$^*$},
title = {{A}nalysis of treatment-free survival of patients with
advanced melanoma receiving nivolumab as monotherapy or in
combination with relatlimab in {RELATIVITY}-047.},
journal = {Journal for ImmunoTherapy of Cancer},
volume = {13},
number = {9},
issn = {2051-1426},
address = {London},
publisher = {BioMed Central},
reportid = {DKFZ-2025-01905},
pages = {e012747},
year = {2025},
abstract = {Treatment-free survival (TFS; time spent free of systemic
anticancer therapy) is increasingly used to support
traditional endpoints. TFS was previously evaluated in
patients with advanced melanoma treated with nivolumab plus
ipilimumab. This analysis compared TFS for nivolumab plus
relatlimab and nivolumab monotherapy in patients with
advanced melanoma.Data were from 714 patients in the phase
2/3 RELATIVITY-047 trial (ClinicalTrials.gov identifier:
NCT03470922). TFS was defined as the difference in
restricted mean event times between the Kaplan-Meier curves
for time to protocol therapy cessation and time to
subsequent systemic anticancer therapy initiation or death.
TFS was further partitioned into time with and time without
grade ≥3 treatment-related adverse events (TRAEs).
Subgroup analysis based on tumor BRAF mutational status and
tumor programmed death ligand 1 (PD-L1) expression level was
conducted. Between-treatment group differences were
calculated with bootstrapped $95\%$ CIs.At 48 months from
randomization, Kaplan-Meier estimates of overall survival
were $52\%$ and $43\%$ for patients in the nivolumab plus
relatlimab and nivolumab groups, respectively; $38\%$ and
$33\%$ of patients in these respective groups were free of
subsequent systemic therapy. The 48-month mean TFS was 2.9
months $(95\%$ CI 1.0 to 4.9) longer with nivolumab plus
relatlimab than with nivolumab (9.7 vs 6.8 months,
respectively). Mean TFS represented $20\%$ and $14\%$ of the
48-month period after initiating nivolumab plus relatlimab
and nivolumab, respectively. Considering only time without
grade ≥3 TRAEs, the 48-month mean TFS was 2.6 months
$(95\%$ CI 0.8 to 4.5) longer with nivolumab plus relatlimab
than with nivolumab (9.1 vs 6.5 months, respectively). The
48-month mean total TFS was consistently longer with
nivolumab plus relatlimab than with nivolumab in the BRAF
mutant (9.4 vs 6.5 months), BRAF wild-type (9.9 vs 6.9
months), PD-L1 $≥1\%$ (12.3 vs 7.7 months), and
$PD-L1<1\%$ (7.9 vs 6.2 months) subgroups.This analysis
demonstrated TFS benefit during the 48 months since
initiating nivolumab plus relatlimab compared with nivolumab
alone in patients with advanced melanoma. A direct
comparison between nivolumab plus relatlimab and nivolumab
plus ipilimumab is needed to determine the differences
between the regimens in TFS and those in traditional
endpoints.},
keywords = {Immune Checkpoint Inhibitor (Other) / Immunotherapy (Other)
/ Skin Cancer (Other)},
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:40940136},
doi = {10.1136/jitc-2025-012747},
url = {https://inrepo02.dkfz.de/record/304582},
}