Efficacy and safety of immunotherapy or antiangiogenic agents-based treatment strategies versus chemotherapy as first-line treatment for extensive-stage small cell lung cancer: A network meta-analysis.

Abstract

e14599 Background: Immunotherapy with chemotherapy is recommended as standard first-line therapy for extensive-stage small lung cancer (ES-SCLC) patients. Recent study suggested that the addition of antiangiogenic tyrosine kinase inhibitor anlotinib to immunotherapy and chemotherapy could further improve survival. However, the addition of bevacizumab failed to improve overall survival. This study aims to compare the efficacy and safety of various combinations. Methods: We searched databases, including PubMed, Web of Science, and Embase, for phase Ⅲ randomized controlled trials (RCTs). The Engauge Digitizer was used to extract survival data, and then using Review Manager to combine studies of the same treatment model. The network meta-analysis was performed by the Bayesian framework. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events of grade 3 or higher (Grade ≥3 AEs) were used to evaluate the efficacy or safety by Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs). Results: A total of 13 RCTs that contained 16 treatment options were included for analysis, and were classified into five types of treatment strategies, including ICI + Chemotherapy (ICI + Chemo), ICI + ICI + Chemotherapy (ICI + ICI + Chemo), ICI + Antiangiogenic agent + Chemotherapy (ICI + Antiangio + Chemo), Antiangiogenic agent + Chemotherapy (Antiangio + Chemo) and Chemotherapy alone (Chemo). ICI + Chemo (HR = 0.71, 95% CI: 0.66-0.76) and ICI + Antiangio + Chemo (HR = 0.71, 95% CI: 0.57-0.87) showed similar efficacy compared with Chemo for the OS. However, ICI + Antiangio + Chemo had the longest PFS (HR = 0.37, 95% CI: 0.18-0.77) and highest ORR (OR = 2.08, 95% CI: 1.03-4.05) compared with Chemo. In terms of safety, all groups had a higher possibility of causing more adverse reactions compared with Chemo, especially for ICI + Antiangio + Chemo (OR = 1.42, 95% CI: 0.63-3.32), but there was no statistical difference. Conclusions: ICI + Antiangio + Chemo has the best survival benefit for patients with ES-SCLC in comparison with other treatment models. And, the toxicity of ICI + Antiangio + Chemo was generally acceptable but needed careful attention. The finding verified the important roles of antiangiogenic agents in the treatment of patients with ES-SCLC. The outcomes of different combinations compared with chemo. 　 HR (95% CI) OR (95% CI) Combination OS PFS ORR AEs ICI+Chemo 0.71(0.66-0.76) 0.62(0.32-1.18) 1.24(0.66-2.12) 1.18(0.65-2.48) ICI+ICI+Chemo 0.80(0.69-0.92) 0.75(0.36-1.58) 1.25(0.64-2.40) 1.31(0.64-2.91) ICI+Antiangio+Chemo 0.71(0.57-0.87) 0.37(0.18-0.77) 2.08(1.03-4.05) 1.42(0.63-3.32) Antiangio+Chemo 0.85(0.72-1.01) 0.57(0.23-1.42) 1.59(0.62-4.14) 1.26(0.48-3.36)