Efficacy and safety of PD-1/PD-L1 inhibitor plus chemotherapy versus chemotherapy alone as first-line treatment for extensive-stage small cell lung cancer: A systematic review and meta-analysis.

Background Immunotherapy has afforded new treatment options for extensive small cell lung cancer (ES-SCLC). However, reports on the effectiveness of immune checkpoint inhibitors (ICIs) combined with chemotherapy on survival in ES-SCLC patients are inconsistent. Therefore, we conducted a meta-analysis on the efficacy and safety of ICI combined with chemotherapy for ES-SCLC. Methods We searched for randomized controlled clinical trials related to first-line treatment of ES-SCLC with ICI combined with chemotherapy in PUBMED, ESMO, ASCO, and WCLC since 2018. The primary outcome was overall survival (OS). Results Four studies were included. Compared to chemotherapy alone, ICI in combination with chemotherapy as first-line treatment reduced the risk of death (hazard ratio [HR]: 0.76; 95% CI: 0.68-0.86;P < 0.00001) and disease progression (HR: 0.76; 95% CI: 0.68-0.84;P < 0.00001). The objective response rate (ORR) with ICI plus chemotherapy was significantly higher than that with chemotherapy alone (HR: 1.10; 95% CI: 1.02-1.19,P= 0.01). The duration of response (DoR) rate at one year was also better with ICI plus chemotherapy (HR: 3.46; 95% CI: 2.24-5.33;P < 0.00001). Security analysis revealed that the incidence of immune-mediated adverse events (imAEs) (HR: 3.77; 95% CI: 1.99-7.15,P< 0.0001) and grade 3/4 imAEs (HR: 7.01; 95% CI: 2.48-19.81;P= 0.0002) increased significantly with ICI plus chemotherapy. Conclusions ICI combined with chemotherapy as first-line treatment can significantly improve the OS and progression-free survival (PFS) of ES-SCLC patients, but the toxicity caused by immunotherapy should be carefully considered. Key points Significant findings of the studyOur meta-analysis shows that PD-L1/PD-1 plus chemotherapy can significantly improve the OS and PFS of ES-SCLC patients when used as first-line therapy. What this study adds This study fills gaps regarding the efficacy of immunotherapy combined with chemotherapy as first-line treatment for ES-SCLC, and provides better evidence for the use of PD-L1/PD-1 immunotherapy plus chemotherapy for patients with ES-SCLC.