Clinical outcomes of PD-1 versus PD-L1 inhibitors combined with chemotherapy as first-line treatment for extensive-stage small cell lung cancer: A propensity score–matched study.

Abstract

e20132 Background: Small cell lung cancer (SCLC) is a highly aggressive malignancy, with approximately two-thirds of patients presenting with metastatic disease at initial diagnosis. Over the past decade, regimen combining platinum–etoposide with programmed cell death protein-1 (PD-1) or programmed cell death ligand-1 (PD-L1) inhibitors has become the standard first-line treatment for patients with extensive-stage SCLC (ES-SCLC). Although multiple phase III randomized trials have demonstrated survival benefits for both PD-1– and PD-L1–based regimens, direct comparative evidence between these two classes of immune checkpoint inhibitors remains limited. We therefore conducted a real-world analysis to compare clinical outcomes associated with PD-1 versus PD-L1 inhibitors combined with chemotherapy as first-line treatment for ES-SCLC. Methods: This study retrospectively analyzed 195 patients with ES-SCLC who received PD-1 inhibitors or PD-L1 inhibitors combined with chemotherapy as initial systemic treatment. The patients were divided into two groups: the PD-1 inhibitor plus chemotherapy group (PD-1 group) and the PD-L1 inhibitor plus chemotherapy group (PD-L1 group). Progression-free survival (PFS) and overall survival (OS) were compared and evaluated using the Kaplan-Meier method and Cox regression analysis. The bias between different groups was minimized using propensity score matching (PSM). Results: Among the included 195 patients, 82 (42.1%) received PD-1 inhibitors combined with chemotherapy and 113 (57.9%) received PD-L1 inhibitors combined with chemotherapy. Patients with ES-SCLC harboring liver metastasis were more likely to receive PD-L1 inhibitors combined with chemotherapy ( P < 0.001), but the baseline characteristics were remained balanced included 68 patients per groups after PSM. The results showed that the PFS and OS of patients in the PD-L1 group were significantly better than those in the PD-1 group before (PFS: 7.63 vs. 13.67 months, P < 0.001. OS: 13.33 vs. 23.17 months, P = 0.013) and after PSM (PFS: 7.40 vs. 16.37 months, P < 0.001. OS: 12.47 vs. 19.80 months, P = 0.020). After adjusting for confounders, regimen of PD-L1 inhibitors combined with chemotherapy was still a significant favorable factor for both PFS (HR = 0.43 [95%CI: 0.29-0.63], P < 0.001) and OS (HR = 0.64 [95%CI: 0.41-0.99], P = 0.043). Conclusions: In this retrospective real-world cohort of patients with extensive-stage small cell lung cancer, PD-L1 inhibitors combined with chemotherapy were associated with longer progression-free and overall survival compared with PD-1–based regimens. Given the retrospective design, these findings should be interpreted with caution and warrant further prospective validation.