Meta-analysis of PD-(L)1 inhibitor plus chemotherapy versus chemotherapy as first-line treatment in extensive-stage small-cell lung cancer.

Abstract

Immunotherapy targeting programmed death 1(PD-1) and its ligand (PD-L1) has been successful in extensive-stage small cell lung cancer (ES-SCLC). However, first-line PD-(L)1 inhibitor combined with chemotherapy (immunochemotherapy) versus chemotherapy has not been well studied. Randomized controlled trials had been searched from PubMed, Embase, and the Cochrane Library until December 29, 2022. Randomized effect consistency models were applied for estimating the pooled hazard ratios (HRs) and odds ratios (ORs). Study outcomes included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), 6-month and 1-year disease progression rate, 1-year and 2-year mortality rate, and Grade ≥3 adverse events (AEs). Six eligible trials with 2600 ES-SCLC patients were included. Compared with chemotherapy, immunochemotherapy significantly improved ORR (OR 1.32, 95% CI 1.07-1.63; p = 0.01), PFS (HR 0.68, 95% CI 0.58-0.78; p < 0.001), and OS (HR 0.72, 96% CI 0.66-0.78, p < 0.001) without increasing Grade ≥3 AEs (p = 0.07). Compared with patients with chemotherapy, the 6-month disease progression rate was reduced by 0.39 (p = 0.01) and the 1-year disease progression rate was reduced by 0.75 (p < 0.001), the 1-year mortality rate was reduced by 0.33 (p < 0.001) and the 2-year mortality rate was reduced by 0.50 (p < 0.001) respectively in patients with immunochemotherapy. However, patients with brain metastases failed to prolong PFS and OS from immunochemotherapy (p > 0.05). Compared with chemotherapy, PD-(L)1 inhibitor plus chemotherapy as first-line treatment could improve the efficacy and prognosis of ES-SCLC patients without more serious side effects. However, more research is needed to validate these results.