Real-world outcomes of immunotherapy in older adults with advanced NSCLC: A retrospective cohort analysis.

e20587 Background: Immunotherapy is a standard first-line treatment for driver gene-negative advanced non-small cell lung cancer (NSCLC). However, older patients are underrepresented in clinical trials. This study investigated real-world efficacy and safety in this population. Methods: Clinical data from 649 patients aged ≥65 years with advanced NSCLC treated at Hunan Cancer Hospital between June 2018 and December 2024 were retrospectively analyzed. Patients received immunotherapy (n = 389: immune checkpoint inhibitor (ICI) plus chemotherapy [ICI-chemotherapy], n = 298; ICI alone, n = 91) or chemotherapy (n = 260). Objective response rates (ORRs), disease control rates (DCRs), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were compared. Cox regression analyses identified independent prognostic factors. Baseline characteristics, including PD-L1 and age, defined subgroups. Results: Immunotherapy yielded higher ORR (44.73% vs. 34.62%, P = 0.010) and DCR (85.60% vs. 76.54%, P = 0.003) than chemotherapy. Median PFS (mPFS, 9.57 vs. 6.30 months, P < 0.001) and OS (mOS, 19.27 vs. 14.13 months, P < 0.001) were longer. ICI-chemotherapy achieved longer mOS than ICI alone (3.3-month improvement; P = 0.043). Patients with PD-L1 tumor proportion scores (TPS) ≥50% had longer mPFS (14.63 months) and OS (31.11 months) than those with PD-L1 TPS < 1% (mPFS: P < 0.001; mOS: P = 0.005). Immunotherapy, baseline Eastern Cooperative Oncology Group performance status 0–1, and PD-L1 TPS ≥50% were independent protective factors; baseline liver metastasis was an adverse factor for PFS. Grade ≥3 non-immune-related AE rates were similar. Combination therapy increased the risk of immune-related pneumonitis but not other high-grade immune-related AEs. Conclusions: First-line immunotherapy significantly improves survival in older patients with advanced NSCLC, with manageable safety.