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

Objective Immune checkpoint inhibitors (ICIs) combined with etoposide-platinum are recommended as the standard first-line therapy for extensive-stage small cell lung cancer (ES-SCLC). Despite the potential of antiangiogenic agents to enhance treatment efficacy, the optimal combination pattern remains unclear. This meta-analysis explores existing treatment strategies involving ICIs or antiangiogenic agents in ES-SCLC. Methods Hazard ratios (HRs) and odds ratios (ORs) were generated by R software. The outcomes of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events of grade 3 or higher (Grade >= 3 AEs) were analyzed. The included trials were classified in terms of different 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 (Chemo). Results A total of 13 randomized controlled trials (RCTs) involving 6,822 patients were included in the analysis. The drug combination patterns included ipilimumab, durvalumab, adebrelimab, atezolizumab, socazolimab, pembrolizumab, serplulimab, tislelizumab, toripalimab, durvalumab + tremelimumab, tiragolumab + atezolizumab, benmelstobart + anlotinib, bevacizumab + atezolizumab, anlotinib, bevacizumab in combination with chemotherapy. The antiangiogenic agent-containing regimen benmelstobart + anlotinib + chemotherapy demonstrated the highest potential to achieve superior PFS and OS versus chemotherapy. The group meta-analysis also showed that ICI + Chemo, ICI + ICI + Chemo, and ICI + Antiangio + Chemo presented significantly better OS. Additionally, ICI + Antiangio + Chemo achieved better PFS with the lowest HR of 0.37 and the best ORR of 2.08 versus chemotherapy. Patients treated with benmelstobart + anlotinib + chemotherapy, durvalumab + tremelimumab + chemotherapy, and anlotinib + chemotherapy experienced a higher likelihood of grade >= 3 AEs. Conclusion For individuals with ES-SCLC, ICI + Antiangio + Chemo was identified as an optimal treatment option due to better OS, PFS, and ORR. Benmelstobart + anlotinib + chemotherapy demonstrated a better survival benefit than chemotherapy. The toxicity of ICI + Antiangio + Chemo was acceptable but needed careful attention. These findings clarified the roles of ICIs and antiangiogenic agent-based treatment strategies in this population.