Effectiveness and Safety of PD-1 Inhibitor Rechallenge After Prior Immunotherapy in Patients Aged ≥ 60 Years with...

Evidence regarding the effectiveness and safety of PD-1 inhibitor rechallenge in older patients with advanced non-small-cell lung cancer (NSCLC) previously exposed to immunotherapy remains limited. This study evaluated the effectiveness and safety of PD-1 inhibitor monotherapy rechallenge in patients aged ≥ 60 years with advanced NSCLC who had previously received immunotherapy.

This single-center retrospective cohort study included 56 patients aged ≥ 60 years with advanced NSCLC who received PD-1 inhibitor monotherapy rechallenge at the Department of Oncology Radiotherapy at the Guilin People's Hospital between January 2019 and March 2025. Objective response rate (ORR) and disease control rate (DCR) were assessed per RECIST 1.1 criteria. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Treatment-related adverse events (TRAEs) were graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

In the full analysis population of 56 patients with five non-evaluable patients counted as non-responders, the ORR and DCR were 21.4% and 58.9%, respectively. The median PFS of the 56 older patients with advanced NSCLC receiving PD-1 inhibitors was 3.9 months (95% CI 1.88-5.92) and median OS was 11.3 months (95% CI 4.78-17.82) from rechallenge of PD-1 inhibitors. The safety profile indicated that TRAEs of any grade occurred in 41 patients (73.2%), most commonly fatigue, decreased appetite, rash, hepatic enzyme elevations, pneumonitis, and hypothyroidism. Grade ≥ 3 TRAEs were detected in 15 patients (26.8%). Immune-related TRAEs were generally manageable with corticosteroids and supportive care.

PD-1 inhibitor rechallenge showed modest antitumor activity and a generally manageable safety profile in this selected cohort of patients aged ≥ 60 years with advanced NSCLC previously exposed to immunotherapy. Given the small sample size, single-center retrospective design, and potential selection bias, these findings should be considered preliminary and require validation in larger multicenter prospective studies.