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

<b>Aim:</b> To identify the optimal first-line treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC). <b>Materials &amp; methods:</b> 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. <b>Results:</b> 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. <b>Conclusion:</b> 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.