Real-world evidence for immunotherapy in the first-line or subsequent-line setting in extensive-stage small-cell lung cancer.

[BACKGROUND] Since the approval of immune checkpoint inhibitors (ICIs) in extensive-stage small-cell lung cancer (ES-SCLC) patients, immunotherapy has been commonly prescribed in first-line and sometimes in subsequent-line treatment in clinical practice. However, real-world data on ICIs in ES-SCLC remain limited.

[OBJECTIVES] To delineate the current therapeutic landscape of ES-SCLC and assess the efficacy and outcomes of immunotherapy in different clinical settings.

[DESIGN AND METHODS] Patients with ES-SCLC who received at least two lines of therapy from February 2020 to February 2024 were retrospectively recruited. All enrolled subjects were divided into two groups, namely "ICIs cohort" and "chemotherapy-only cohort" according to the treatment regimens they received in the entire disease course. Patients in the ICIs cohort who received immunotherapy as first-line treatment were analyzed separately from those who received it in later lines. Survival analysis was conducted to evaluate the clinical significance of ICIs in different treatment settings using the Kaplan-Meier method. The utility of thoracic radiotherapy was also evaluated in ES-SCLC patients. Multivariate Cox regression was applied to identify independent predictors of survival in ES-SCLC.

[RESULTS] A total of 214 patients were enrolled during the timeframe, of whom 81 received ICIs in first-line treatment and 78 received ICIs in subsequent-line treatment. In survival analysis, the ICIs cohort demonstrated significantly longer overall survival (OS) than the chemotherapy-only cohort, both in the first-line (17.0 vs 14.27 months;  = 0.045) and subsequent-line settings (16.87 vs 14.27 months;  = 0.017). In addition, the median OS was significantly prolonged in patients who underwent local thoracic radiotherapy compared to those who did not (20.53 vs 14.63 months;  = 0.005). Multivariate survival analysis validated that liver metastasis independently predicts inferior survival ( < 0.001). Meanwhile, immunotherapy administration ( = 0.002) and thoracic radiotherapy ( = 0.036) emerged as significant independent prognostic factors for prolonged survival in ES-SCLC patients.

[CONCLUSION] The incorporation of immunotherapy, either in first-line or subsequent-line treatment, significantly improved survival outcomes in ES-SCLC. Notably, local thoracic radiotherapy retained its significant survival benefit in ES-SCLC in the immunotherapy era.