Real-world evidence of immunotherapy in older adults with advanced non-small cell lung cancer: a retrospective cohort study

Older patients are underrepresented in clinical trials of immunotherapy for driver gene-negative advanced non-small cell lung cancer (NSCLC). This study aimed to investigate real-world efficacy and safety of immunotherapy in this population. Clinical data from 649 patients aged ≥ 65 years with advanced NSCLC were retrospectively analyzed. Patients received either first-line immunotherapy ( n = 389), including Immune checkpoint inhibitor (ICI) plus chemotherapy ( n = 298) and ICI monotherapy ( n = 91), or chemotherapy ( n = 260). Objective response rates (ORRs), disease control rates (DCRs), progression-free survival (PFS), overall survival (OS), and adverse events were compared. Cox regression analyses identified independent prognostic factors. Immunotherapy yielded higher ORR (44.73% vs. 31.54%, P = 0.001) and DCR (85.60% vs. 76.54%, P = 0.003) than did chemotherapy. The median PFS and OS in the Immunotherapy group were 9.57 and 19.27 months, respectively; mOS in the ICI-Chemotherapy group was significantly longer by 3.3 months compared with the ICI-alone group ( P = 0.043). Among the immunotherapy cohort with available PD-L1 expression data ( n = 218), PD-L1 TPS ≥ 50% consistently demonstrated better outcomes than TPS < 1%. In the overall cohort, immunotherapy and baseline ECOG PS 0–1 were protective factors for PFS and OS, whereas baseline liver metastasis was a risk factor for PFS only. Regarding safety, the incidence of any-grade Treatment-related adverse events (TRAEs) (62.2% vs. 68.1%) and grade ≥ 3 TRAEs (37.5% vs. 40.0%) did not differ significantly between the Immunotherapy and Chemotherapy groups. First-line immunotherapy significantly improves survival in older patients with advanced NSCLC. Immunotherapy plus chemotherapy is superior to immunotherapy alone regarding OS, with manageable safety.