Amanda Tufman1, Jens Neumann2, Farkhad Manapov3, Laura Sellmer4, Andreas Jung5, Diego Kauffmann-Guerrero6, Kathrin Kahnert7, Pontus Mertsch8, Astrid Borgmeier9, Sabine Semrau10, Achim Rittmeyer11, Bernhard Ulm12, Kurt Ulm13, Michael Flentje14, Rainer Fietkau15, Rudolf Maria Huber16. 1. Department of Internal Medicine V, Thoracic Oncology Centre Munich, LMU Munich, Ziemssenstr. 1, 80336 Munich, Germany; Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Max-Lebsche-Platz 31, 81377 Munich, Germany. Electronic address: Amanda.Tufman@med.uni-muenchen.de. 2. Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany. Electronic address: Jens.Neumann@med.uni-muenchen.de. 3. Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany. Electronic address: Farkhad.Manapov@med.uni-muenchen.de. 4. Department of Internal Medicine V, Thoracic Oncology Centre Munich, LMU Munich, Ziemssenstr. 1, 80336 Munich, Germany; Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Max-Lebsche-Platz 31, 81377 Munich, Germany. Electronic address: Laura.Sellmer@med.uni-muenchen.de. 5. Institute of Pathology, Faculty of Medicine, LMU Munich, Thalkirchner Str. 36, 80337 Munich, Germany. Electronic address: Andreas.Jung@med.uni-muenchen.de. 6. Department of Internal Medicine V, Thoracic Oncology Centre Munich, LMU Munich, Ziemssenstr. 1, 80336 Munich, Germany; Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Max-Lebsche-Platz 31, 81377 Munich, Germany. Electronic address: Diego.KauffmannGuerrero@med.uni-muenchen.de. 7. Department of Internal Medicine V, Thoracic Oncology Centre Munich, LMU Munich, Ziemssenstr. 1, 80336 Munich, Germany; Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Max-Lebsche-Platz 31, 81377 Munich, Germany. Electronic address: Kathrin.Kahnert@med.uni-muenchen.de. 8. Department of Internal Medicine V, Thoracic Oncology Centre Munich, LMU Munich, Ziemssenstr. 1, 80336 Munich, Germany; Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Max-Lebsche-Platz 31, 81377 Munich, Germany. Electronic address: Pontus.Mertsch@med.uni-muenchen.de. 9. Department of Internal Medicine V, Thoracic Oncology Centre Munich, LMU Munich, Ziemssenstr. 1, 80336 Munich, Germany; Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Max-Lebsche-Platz 31, 81377 Munich, Germany. Electronic address: Astrid.Borgmeier@med.uni-muenchen.de. 10. Department of Radiation Oncology, University Hospital Erlangen, Universitätsstr. 27, 91054 Erlangen, Germany. Electronic address: Sabine.Semrau@uk-erlangen.de. 11. Department of Pneumology, Lung Clinic Immenhausen, Robert-Koch-Str. 3, 34376 Immenhausen, Germany. Electronic address: arittmeyer@lungenfachklinik-immenhausen.de. 12. Department of Anaesthesiology and Intensive Care Medicine, School of Medicine, Technical University of Munich, Munich, Germany. Electronic address: Bernhard.ulm@tum.de. 13. Institute of Medical Informatics, Statistics and Epidemiology, Technical University of Munich, Ismaninger Str 22, 81675 Munich, Germany. Electronic address: kurt.ulm@tum.de. 14. Department of Radiation Oncology, University Hospital Würzburg, Josef-Schneider Str. 2, 97080 Würzburg, Germany. Electronic address: flentje_m@ukw.de. 15. Department of Radiation Oncology, University Hospital Erlangen, Universitätsstr. 27, 91054 Erlangen, Germany. Electronic address: Rainer.Fietkau@uk-erlangen.de. 16. Department of Internal Medicine V, Thoracic Oncology Centre Munich, LMU Munich, Ziemssenstr. 1, 80336 Munich, Germany; Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Max-Lebsche-Platz 31, 81377 Munich, Germany. Electronic address: Huber@med.uni-meunchen.de.
Abstract
OBJECTIVES: Immune checkpoint inhibition after radiochemotherapy (RTCT) has become a new standard of care for locally advanced non-small cell lung cancer with programmed death-ligand 1 (PD-L1) expression. However, little is known about the prognostic role of immune response markers in this setting. We analysed PD-L1 expression and tumour infiltrating lymphocytes (TiLs) in tumour biopsies from the multicenter German Intergroup Lung Trial (GILT), which previously randomised patients with stage III NSCLC to RTCT with or without consolidation chemotherapy. MATERIALS AND METHODS: We retrospectively analyzed tumour biopsies from patients treated in the GILT trial. PD-L1 expression was analysed using the Ventana SP263 assay and TiL score (low, intermediate, high) and pattern (excluded, inflamed, desert) were assessed. The primary endpoint of the biomarker analysis was PFS in patients with PD-L1 ≥ 1% vs. PD-L1 < 1% NSCLC. Secondary endpoints explored the prognostic relevance of additional PD-L1 expression levels and TiL score and pattern. RESULTS: Biopsies were available from 92 patients treated with RTCT. Patients with available tumor tissue did not differ significantly from the whole study population. PD-L1 scores from 78 samples were available for analysis. There was no difference in PFS in the PD-L1 < 1% vs. PD-L1 ≥ 1% subgroups. TiL score was available in 66 patients. Patients with high TiL score showed favourable overall survival compared to the low TiL subgroup. This trend was most pronounced in those patients treated with consolidative chemotherapy. CONCLUSION: In this analysis, PD-L1 expression did not correlate with PFS following RTCT. However, patients with TiLs > 10% were found to have longer overall survival, especially for those patients treated with consolidation chemotherapy after the end of RTCT. Further analyses to explore the prognostic and predictive relevance of TiLs in the context of consolidative checkpoint inhibition with durvalumab are required.
OBJECTIVES: Immune checkpoint inhibition after radiochemotherapy (RTCT) has become a new standard of care for locally advanced non-small cell lung cancer with programmed death-ligand 1 (PD-L1) expression. However, little is known about the prognostic role of immune response markers in this setting. We analysed PD-L1 expression and tumour infiltrating lymphocytes (TiLs) in tumour biopsies from the multicenter German Intergroup Lung Trial (GILT), which previously randomised patients with stage III NSCLC to RTCT with or without consolidation chemotherapy. MATERIALS AND METHODS: We retrospectively analyzed tumour biopsies from patients treated in the GILT trial. PD-L1 expression was analysed using the Ventana SP263 assay and TiL score (low, intermediate, high) and pattern (excluded, inflamed, desert) were assessed. The primary endpoint of the biomarker analysis was PFS in patients with PD-L1 ≥ 1% vs. PD-L1 < 1% NSCLC. Secondary endpoints explored the prognostic relevance of additional PD-L1 expression levels and TiL score and pattern. RESULTS: Biopsies were available from 92 patients treated with RTCT. Patients with available tumor tissue did not differ significantly from the whole study population. PD-L1 scores from 78 samples were available for analysis. There was no difference in PFS in the PD-L1 < 1% vs. PD-L1 ≥ 1% subgroups. TiL score was available in 66 patients. Patients with high TiL score showed favourable overall survival compared to the low TiL subgroup. This trend was most pronounced in those patients treated with consolidative chemotherapy. CONCLUSION: In this analysis, PD-L1 expression did not correlate with PFS following RTCT. However, patients with TiLs > 10% were found to have longer overall survival, especially for those patients treated with consolidation chemotherapy after the end of RTCT. Further analyses to explore the prognostic and predictive relevance of TiLs in the context of consolidative checkpoint inhibition with durvalumab are required.