Efficacy and safety of PD-L1 inhibitors versus PD-1 inhibitors in first-line treatment with chemotherapy for extensive-stage small-cell lung cancer

Abstract

Programmed cell death-ligand 1 inhibitors plus chemotherapy (PD-L1\u2009+\u2009Chemo) have achieved substantial progress in extensive-stage small-cell lung cancer (ES-SCLC). However, evidence about programmed cell death 1 inhibitors plus chemotherapy (PD-1\u2009+\u2009Chemo) in SCLC is relatively lacking. Whether PD-1 inhibitors differ from PD-L1 inhibitors in their clinical outcomes remains controversial. We performed a meta-analysis to compare efficacy and safety of PD-L1\u2009+\u2009Chemo vs PD-1\u2009+\u2009Chemo in ES-SCLC by searching PubMed, Embase, the Cochrane Library, and major oncology conferences. We examined overall survival (OS) as the primary outcome. Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (AEs). We included four randomized trials (IMpower133, CASPIAN, KEYNOTE-604, and EA5161) with a total of 1553 patients. Direct comparison showed that PD-L1\u2009+\u2009Chemo (PFS: hazard ratio [HR] 0.79; OS: HR 0.75) and PD-1\u2009+\u2009Chemo (PFS: HR 0.72; OS: HR 0.77) significantly prolonged survival time compared with chemotherapy alone. But PD-L1\u2009+\u2009Chemo (relative risk [RR]: 1.07) and PD-1\u2009+\u2009Chemo (RR: 1.13) were not superior to chemotherapy alone in terms of ORR. Indirect comparison showed no significant difference in clinical efficacy between PD-L1\u2009+\u2009Chemo and PD-1\u2009+\u2009Chemo (OS: HR 0.99; PFS: HR 1.10; ORR: RR 0.95). We further stratified patients according to subgroups in terms of OS. In the subgroup of patients with brain metastasis, PD-L1\u2009+\u2009Chemo tended to prolong OS (HR: 0.61, 0.28 to 1.32). There were no significant differences between PD-L1\u2009+\u2009Chemo and PD-1\u2009+\u2009Chemo regarding safety analyses. However, PD-L1\u2009+\u2009Chemo exhibited a better safety profile in reducing the risk of treatment discontinuation due to AEs (RR: 0.43, 0.19 to 0.95) and pneumonia (pneumonia of any grade, RR: 0.59, 0.24 to 1.42; pneumonia of grade\u2009≥\u20093, RR: 0.37, 0.10 to 1.39). PD-L1\u2009+\u2009Chemo and PD-1\u2009+\u2009Chemo provided a significant survival benefit relative to chemotherapy alone for ES-SCLC. The efficacy and safety of PD-L1\u2009+\u2009Chemo and PD-1\u2009+\u2009Chemo were similar based on current evidence.