Reconsidering 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)

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.

Authors

Institutions

Publication Details

Journal
Clinical & Experimental Metastasis
Published
2025-07-24
DOI
https://doi.org/10.1007/s10585-025-10358-x
Citations
1
Primary Topic
Cancer Immunotherapy and Biomarkers
Type
article
Field-Weighted Citation Impact
1.05

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Reconsidering 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)

Rouven Behnisch, Thomas Wiegel, S. Wetzel, Akin Atmaca et al.
1 citations
Clinical & Experimental Metastasis
Cancer Immunotherapy and Biomarkers
1.05
article

Reconsidering 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)

Rouven Behnisch, Thomas Wiegel, S. Wetzel, Akin Atmaca, Martin Faehling, Farastuk Bozorgmehr, Florian Würschmidt, Christina Kopp, Sven Henschke, Martin Wermke, Florian Sterzing, Alev Petroff, Dirk Bottke, Michaela Hammer‐Hellmig, Constantin Schwab, Martin Reck, Andrej Stupavsky, Jelena Cvetković, R. Krempien, Niels Reinmuth, Jürgen R. Fischer, Farkhad Manapov, Marc Bischof, Christian Schumann, Jürgen Debus, Walburga Engel-Riedel, Stefan Rieken, Esther G.C. Troost, Michael Thomas, Jochen Fleckenstein, Lena Brückner, Helge Schröder, Albrecht Stenzinger, Petros Christopoulos, Inn Chung, Thorsten Götze, Cornelia Kropf-Sanchen, Bernd Schmidt, Christian Grohé
article en
1 citations

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.

Clinical & Experimental MetastasisVol. 42(5)
Goethe University Frankfurt (DE), Heidelberg University (DE), University Hospital Heidelberg (DE), Kempten University of Applied Sciences (DE), LMU Klinikum (DE), Zimmer Biomet (Germany) (DE), National Center for Tumor Diseases (DE), Klinikum Esslingen (DE), Asklepios Fachkliniken München-Gauting (DE), AIO Studien gGmbH (DE), German Center for Lung Research (DE), University Hospital Frankfurt (DE), DRK Kliniken Berlin (DE), Krankenhaus Nordwest (DE), Klinik Blankenstein (DE), LungenClinic Grosshansdorf (DE), Evangelische Lungenklinik Berlin (DE), University Hospital Cologne (DE), University Hospital Ulm (DE), SLK-Kliniken Heilbronn (DE), Helios Hospital Berlin-Buch (DE), University Hospital Carl Gustav Carus (DE), University of Göttingen (DE), Ludwig-Maximilians-Universität München (DE), Saarland University (DE)
Bristol-Myers Squibb, AIO-Studien, Universitätsklinikum Heidelberg
No poverty
Openalex Percentile: Top 19%
Cancer Immunotherapy and Biomarkers
1.05
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.