Prognostic and predictive value of PD-L1 expression and tumour infiltrating lymphocytes (TiLs) in locally advanced NSCLC treated with simultaneous radiochemotherapy in the randomized, multicenter, phase III German Intergroup lung Trial (GILT). (October 2021)

• Record Type: Journal Article
• Authors: Tufman, Amanda; Neumann, Jens; Manapov, Farkhad; Sellmer, Laura; Jung, Andreas; Kauffmann-Guerrero, Diego; Kahnert, Kathrin; Mertsch, Pontus; Borgmeier, Astrid; Semrau, Sabine; Rittmeyer, Achim; Ulm, Bernhard; Ulm, Kurt; Flentje, Michael; Fietkau, Rainer; Huber, Rudolf Maria
• Is Part Of: Lung cancer. Volume 160(2021)
• Page Start: 17
• Page End: 27
• Publication Date: 2021-10
• Subjects: TiLs -- PDL1 -- Chemoradiotherapy -- Prognostic factors -- Checkpoint inhibition; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2021.07.008
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Tumor biopsies from the multicenter German Intergroup Lung Trial of radiochemotherapy followed by consolidation chemotherapy were available for PD-L1 and TiL analysis. Tumor PD-L1 expression did not correlate with progression free survival or overall survival following RTCT for inoperable stage III NSCLC. Tumor infiltrating lymphocyte (TiLs) score correlated with longer overall survival following RTCT for inoperable stage III NSCLC, in particular for patients treated with consolidation chemotherapy. TiL score and TiL pattern did not correlate with differences in progression free survival. 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.