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

Chengjun Wang¹chuang yang¹wen zhao¹Rongyu Zhang¹Tiantian Xuan²Jisheng Li^1*

• ¹Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China., Jinan, Shandong, China
• ²Department of Medical Oncology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, China., Qingdao, Shandong, China

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 aims to explore the existing treatment strategies involving ICIs or antiangiogenic agents in ES-SCLC.Methods: Hazard ratios (HRs) and odds ratios (ORs) were generated by the ‘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 into groups 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: Totally 13 randomized controlled trials (RCTs) involving 6822 patients were included. 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 suffered higher likelihood of grade ≥3 AEs without unexpected AEs.Conclusion: For individuals with ES-SCLC, ICI + Antiangio + Chemo was identified as optimal treatment options on account of better OS, PFS and ORR. Benmelstobart + anlotinib + chemotherapy demonstrated best survival benefit compared to chemotherapy. The toxicity of ICI + Antiangio + Chemo was acceptable but needed careful attention. These findings clarified the roles of ICIs and antiangiogenic agents-based treatment strategies in this population.