Real-world evaluation of immunotherapy in multi-line treatment of small cell lung cancer.

[OBJECTIVE] To assess the real-world efficacy and safety of immunotherapy in small cell lung cancer (SCLC) across multiple lines of treatment.

[METHODS] We conducted a single-center, retrospective cohort study analyzing clinical data from 397 SCLC patients treated at the Second People's Hospital of Yichang (January 2018-July 2024). Based on treatment strategies, patients were divided into four groups: (1) first-line immune checkpoint inhibitor (ICIs)-based combination therapy, (2) first-line chemotherapy, (3) later-line ICIs-based combination therapy after first-line chemotherapy, and (4) chemotherapy in all lines. Propensity score matching (PSM) was used to balance baseline characteristics. Survival outcomes and safety were evaluated.

[RESULTS] After matching, baseline characteristics were comparable. In patients with extensive-stage SCLC (ES-SCLC), first-line ICIs‑based combination therapy significantly improved median overall survival (OS, 12.9 vs. 10.2 months; hazard ratio [HR] = 0.56, 95% CI 0.38-0.80;  = 0.00189) and median progression-free survival (PFS, 8.0 vs. 5.6 months; HR = 0.57, 95% CI 0.40-0.80;  = 0.00125) compared with chemotherapy alone. In the limited-stage cohort, first-line ICIs‑based combination therapy yielded numerically longer OSOS (40.0 vs. 15.5 months;  = 0.121), though results are preliminary and should be interpreted with caution given sample limitations. In the later-line setting, ICIs‑based combination therapy significantly extended median OS compared with chemotherapy (10.4 vs. 7.4 months; HR = 0.60, 95% CI 0.37-0.98;  = 0.0405). Exploratory analysis indicated longer OS with later-line versus first-line ICIs (22.6 vs. 12.6 months; HR = 2.44, 95% CI 1.12-5.33;  = 0.0255); however, this finding may be influenced by potential selection biases and guarantee-time bias and should be viewed as hypothesis-generating only. Immune-related adverse events (irAEs) occurred in 11.1-22.2%, indicating manageable toxicity.

[CONCLUSION] Immunotherapy, whether first-line or later-line, improves survival in ES-SCLC with acceptable safety. Our exploratory results suggest that later-line immunotherapy may be associated with favorable survival trends; however, these findings are hypothesis-generating and require validation in prospective trials due to inherent selection biases.