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.

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.