Beyond-line immunotherapy in ES-SCLC: Efficacy and safety of second-line PD-1/PD-L1 inhibitors after progression on first-line PD-1/PD-L1 inhibitors plus platinum-etoposide chemotherapy.

Abstract

e20149 Background: While Programmed Death-1/Programmed Death-Ligand 1(PD-1/PD-L1) inhibitors combined with platinum-etoposide are the standard first-line treatment for extensive-stage small cell lung cancer (ES-SCLC), optimal second-line strategies remain poorly defined. Evidence regarding the clinical benefit of continuing immunotherapy beyond progression (IBP) is lacking. This study evaluated the efficacy and safety of second-line PD-1/PD-L1 inhibition following progression on first-line immunochemotherapy. Methods: We retrospectively analyzed 96 patients with ES-SCLC who progressed after first-line PD-1/PD-L1 inhibitors plus EP/EC chemotherapy at The First Affiliated Hospital of Dalian Medical University between January 2020 and March 2025. Patients were categorized into two groups: the IBP group (n = 55), receiving continuous PD-1/PD-L1 inhibitors as second-line therapy, and the Non-IBP group (n = 41). Survival outcomes were compared using Kaplan-Meier curves and Cox proportional hazards models. Results: The IBP group demonstrated numerically higher objective response rates (ORR: 28.30% vs. 16.28%, p = 0.2231) and disease control rates (DCR: 69.81% vs. 58.14%, p = 0.2854) compared to the non-IBP group. Notably, IBP was associated with significantly prolonged median progression-free survival (mPFS: 4.3 vs. 2.2 months; HR = 0.59; 95% CI, 0.38–0.94; p = 0.0118) and median overall survival (mOS: 12.5 vs. 6.8 months; HR = 0.56; 95% CI, 0.34–0.92; p = 0.0120). Subgroup analyses revealed significant PFS benefits for IBP in patients who were male, aged < 65 years, had ECOG PS 1, involvement of > 3 metastatic organs, liver/brain metastases, absence of bone metastases, new lesions at progression, > 4 cycles of first-line therapy, first-line clinical benefit (PR/CR/SD), first-line PFS > 3 months, and the use of irinotecan-based second-line regimens. Furthermore, the OS benefit remained robust in patients who were male, had ECOG PS 1, involvement of > 3 metastatic organs, liver/brain metastases, > 4 cycles of first-line therapy, first-line clinical benefit (PR/CR/SD) and first-line PFS > 3 months. The safety profile of IBP was manageable, with no new safety signals. Conclusions: Second-line PD-1/PD-L1 inhibitors beyond progression significantly improved PFS and OS in ES-SCLC. These findings suggest that continuing PD-1/PD-L1 inhibition is a promising strategy for specific patient populations, especially those with high metastatic burden or favorable response to initial immunotherapy.