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@ARTICLE{Bozorgmehr:303122,
author = {F. Bozorgmehr and I. Chung and J. R. Fischer and M. Bischof
and A. Atmaca and S. Wetzel and M. Faehling and D. Bottke
and M. Wermke$^*$ and E. G. C. Troost and C. Kropf-Sanchen
and T. Wiegel and B. Schmidt and A. Stupavsky and W.
Engel-Riedel and M. Hammer-Hellmig and N. Reinmuth and F.
Manapov and C. Grohe and R. Krempien and C. Schumann and F.
Sterzing and M. Reck and F. Würschmidt and J. Fleckenstein
and A. Petroff and S. Henschke and R. Behnisch and J.
Cvetkovic and L. Brückner and C. Schwab and A. Stenzinger
and T. Götze and C. Kopp and H. Schröder and J. Debus and
P. Christopoulos and M. Thomas and S. Rieken},
title = {{R}econsidering palliative radiotherapy in addition to
{PD}-1 blockade for non-small cell lung cancer: results from
the {FORCE} phase {II} trial ({AIO}/{YMO}-{TRK}-0415).},
journal = {Clinical $\&$ experimental metastasis},
volume = {42},
number = {5},
issn = {0262-0898},
address = {Dordrecht},
publisher = {Springer Science + Business Media B.V.},
reportid = {DKFZ-2025-01541},
pages = {42},
year = {2025},
abstract = {Introduction of immune checkpoint inhibitors (ICI) has
improved overall survival (OS) for advanced non-small cell
lung cancer (NSCLC). However, responses differ greatly
amongst patients. Additional radiotherapy (RT) may promote
tumor-specific immunity and synergize with ICI to improve
tumor control. The multicenter phase II FORCE trial
evaluated safety and efficacy of nivolumab with additional
palliative radiotherapy (5 × 4 Gy) as clinically indicated
in pre-treated metastatic non-squamous NSCLC (group A, n =
41), including pretreated patients without an indication for
radiotherapy in a parallel cohort as real-world controls
(group B, n = 60). With an objective response rate (ORR) of
$8.3\%$ in group A (n = 41), the primary endpoint was not
met (p = 0.991). ORR in group B (n = 60) was $23.8\%.$
Patient characteristics indicated a significantly poorer
baseline clinical condition for group A compared to B,
including worse Eastern Cooperative Oncology Group (ECOG)
performance status (PS, p = 0.020) and more metastatic sites
(p = 0.009). Consequently, group A had shorter
progression-free survival (median PFS, 1.9 versus 3.7
months, hazard ratio [HR] 1.69 $[95\%$ CI (1.10, 2.58)]) and
OS (median 6.0 versus 12.6 months, HR 1.75 $[95\%$ CI (1.07,
2.84)]). In multivariable analyses for the
intention-to-treat (ITT) population, ORR, PFS and OS were
inversely associated with the patients' ECOG PS (ORR odds
ratio [OR] 0.126, p = 0.004) and correlated positively with
tumor PD-L1 expression (ORR OR 12.8, p = 0.022), but not
with radiotherapy administration (p = 0.169-0.854). Adverse
events were distributed equally in both groups. Addition of
palliative radiotherapy to nivolumab was safe and feasible,
but not associated with improved efficacy. Patients with an
indication for palliative radiotherapy have an inherently
worse prognosis which cannot be overcome by
radiation-induced immunostimulation. Clinical features and
PD-L1 expression influence clinical outcomes more than
radiotherapy administration and should be considered when
evaluating the effectiveness of immuno-/radiotherapy
combinations.ClinicalTrials.gov identifier: NCT03044626.},
keywords = {Humans / Carcinoma, Non-Small-Cell Lung: therapy /
Carcinoma, Non-Small-Cell Lung: pathology / Carcinoma,
Non-Small-Cell Lung: mortality / Carcinoma, Non-Small-Cell
Lung: drug therapy / Male / Female / Lung Neoplasms:
pathology / Lung Neoplasms: therapy / Lung Neoplasms:
mortality / Lung Neoplasms: drug therapy / Aged / Middle
Aged / Immune Checkpoint Inhibitors: therapeutic use /
Palliative Care: methods / Nivolumab: therapeutic use /
Programmed Cell Death 1 Receptor: antagonists $\&$
inhibitors / Aged, 80 and over / Adult / Immunotherapy
(Other) / Nivolumab (Other) / Non-small cell lung cancer
(Other) / Palliative radiotherapy (Other) /
Radioimmunotherapy (Other) / Immune Checkpoint Inhibitors
(NLM Chemicals) / Nivolumab (NLM Chemicals) / Programmed
Cell Death 1 Receptor (NLM Chemicals) / PDCD1 protein, human
(NLM Chemicals)},
cin = {DD01},
ddc = {610},
cid = {I:(DE-He78)DD01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40702361},
pmc = {pmc:PMC12287132},
doi = {10.1007/s10585-025-10358-x},
url = {https://inrepo02.dkfz.de/record/303122},
}