Tumor immunophenotypic correlates in patients aged 80 years or older with non-small cell lung cancer and outcomes to first-line pembrolizumab in PD-L1 high (≥50%) patients Journal Article

  

Authors:	Barrichello, A. P. C.; Elkrief, A.; Ricciuti, B.; Ganta, T.; Marron, T. U.; Wang, X.; Lotter, W.; Lindsay, J.; Santo, V.; Cortellini, A.; Sharma, B.; Felt, K.; Pfaff, K.; Lamberti, G.; Pecci, F.; Federico, A. D.; Makarem, M.; Gandhi, M. M.; Nguyen, T.; Haradon, D.; Vaz, V. R.; Johnson, B. E.; Debnath, N.; Wang, Y.; Kuang, A. G.; Saeed, A.; Radford, M.; Lovly, C. M.; Nebhan, C. A.; Pinato, D. J.; Rodig, S. J.; Schoenfeld, A. J.; Awad, M. M.; Alessi, J. V.; Naqash, A. R.
Article Title:	Tumor immunophenotypic correlates in patients aged 80 years or older with non-small cell lung cancer and outcomes to first-line pembrolizumab in PD-L1 high (≥50%) patients
Abstract:	Background: Non-small cell lung cancer (NSCLC) patients aged ≥80 years [y] are underrepresented in clinical trials. We evaluated whether age correlates with a distinct immunophenotype or impacts outcomes to first-line pembrolizumab in patients with advanced NSCLC, PD-L1 Tumor Proportion Score (TPS) of ≥50%, and aged ≥80y. Methods: Three NSCLC cohorts were retrospectively analyzed to assess the impact of age (<80y versus ≥80y) on pembrolizumab efficacy and the tumor microenvironment (TME). Cohort A encompassed patients receiving first-line pembrolizumab for advanced NSCLC with PD-L1 ≥50%. Cohort B comprised patients with tumor profiling using multiplexed immunofluorescence (ImmunoPROFILE). Cohort C included The Cancer Genome Atlas (TCGA) and Stand Up to Cancer (SU2C) databases for gene expression analysis. Results: In Cohort A (N = 669), patients ≥80y (N = 111) showed no significant differences in objective response rate or median progression-free survival compared to younger patients (N = 558), but had shorter median overall survival and were less likely to receive second-line therapy after progression on pembrolizumab. In Cohort B (N = 567), tumors from patients ≥80y (N = 45) exhibited higher intratumoral FOXP3+ T cells and closer vicinity of PD-1+ immune cells to tumor cells compared to <80y (N = 522). Cohort C revealed a distinct immunophenotype in samples from patients ≥ 80y, with elevated specific immune cell subsets and up-regulated immune checkpoint proteins. Conclusion: Patients ≥80y with PD-L1-high NSCLC displayed a distinct immunophenotype in the TME but achieved similar ORR and mPFS with first-line pembrolizumab compared to younger patients. OS was shorter in older patients, who were less likely to receive second-line therapy. © 2025 Elsevier Inc.
Keywords:	immunotherapy; tumor microenvironment; older adults; immune cells; thoracic tumors
Journal Title:	Clinical Lung Cancer
Volume:	26
Issue:	4
ISSN:	1525-7304
Publisher:	Elsevier Inc.
Date Published:	2025-06-01
Start Page:	288
End Page:	298.e8
Language:	English
DOI:	10.1016/j.cllc.2025.01.014
PUBMED:	40021433
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85219101553&doi=10.1016%2fj.cllc.2025.01.014&partnerID=40&md5=eb2c61af3e64ba4a06460d67b7b3cd7f
Notes:	Article -- Source: Scopus

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