Navigating first-line therapies for extensive-stage small-cell lung cancer: a frequentist network meta-analysis and systematic review

Aim: To identify the optimal first-line treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC). Materials & methods: We conducted a network meta-analysis (CRD42023486863) to systematically evaluate the efficacy and safety of eight first-line treatment regimens for ES-SCLC, including 15 clinical trials. Results: Our analysis showed that the PD-1/PD-L1 + etoposide combined with platinum (EP) and PD-L1 + vascular endothelial growth factor (VEGF) + EP regimens significantly enhanced overall survival and progression-free survival, with subgroup analysis revealing that serplulimab ranked as the most promising option for improving overall survival. Integrating anti-angiogenesis drugs into immunochemotherapy presents potential benefits, with an increased incidence of adverse events necessitating further investigation. Conclusion: Our findings offer valuable insights for future research and for developing more effective treatment strategies for ES-SCLC, underscoring the critical need for continued innovation in this therapeutic area. Immunochemotherapy has changed the treatment landscape of extensive-stage small-cell lung cancer (ES-SCLC), but the efficacy of this strategy still needs improvement. Compared with chemotherapy, immunochemotherapy has demonstrated a significantly enhanced overall survival (OS) and progression-free survival in patients with ES-SCLC. Furthermore, integrating anti-angiogenesis drugs into immunochemotherapy regimens has shown an additional benefit. The efficacy and safety of PD-1 inhibitors and PD-L1 inhibitors have no significant difference. Serplulimab ranked as the most promising option combined with chemotherapy for improving the OS of ES-SCLC patients. Combining anti-angiogenesis targeted therapy with immunochemotherapy presents a promising direction for future studies, which need further exploration. Notably, combining anti-angiogenesis targeted therapy with immunochemotherapy was associated with increased grade ≥3 TRAEs. Our study indicated multidisciplinary treatment strategies that could potentially transform the therapeutic landscape for ES-SCLC, underscoring the need for continued innovation and research in this field. The findings have significant implications for clinical decision-making, potentially guiding the development of more effective treatment strategies for this highly challenging form of lung cancer.

研究目的：旨在明确广泛期小细胞肺癌（extensive-stage small-cell lung cancer, ES-SCLC）患者的最优一线治疗方案。材料与方法：本研究开展了一项网状Meta分析（CRD42023486863），系统评价了8种针对ES-SCLC的一线治疗方案的疗效与安全性，共纳入15项临床试验。研究结果：本分析显示，PD-1/PD-L1抑制剂联合EP方案（依托泊苷联合铂类）以及PD-L1抑制剂联合血管内皮生长因子（vascular endothelial growth factor, VEGF）联合EP方案可显著延长患者的总生存期与无进展生存期；亚组分析结果表明，斯鲁利单抗（serplulimab）在改善患者总生存期方面位列最具前景的候选方案。将抗血管生成药物整合至免疫化疗方案中具有潜在获益，但不良事件发生率升高的问题仍需进一步研究探讨。结论：本研究结果可为ES-SCLC的后续研究及更高效治疗策略的开发提供重要参考，凸显了该治疗领域持续创新的关键必要性。免疫化疗已改变了广泛期小细胞肺癌的治疗格局，但该策略的疗效仍有待提升。与单纯化疗相比，免疫化疗可显著改善ES-SCLC患者的总生存期（overall survival, OS）与无进展生存期（progression-free survival, PFS）。此外，在免疫化疗方案中加入抗血管生成药物可带来额外获益。PD-1抑制剂与PD-L1抑制剂的疗效与安全性无显著差异。斯鲁利单抗联合化疗方案在改善ES-SCLC患者总生存期方面为最具前景的选择。将抗血管生成靶向治疗与免疫化疗联合是未来研究的极具潜力的方向，有待进一步探索。值得注意的是，抗血管生成靶向治疗联合免疫化疗与≥3级治疗相关不良事件（treatment-related adverse events, TRAEs）发生率升高相关。本研究表明，多学科治疗策略有望重塑ES-SCLC的治疗格局，凸显了该领域持续创新与研究的必要性。本研究结果对临床决策具有重要指导意义，可为这种极具挑战性的肺癌类型开发更有效的治疗方案提供参考。