Efficacy and safety of first-line immunotherapy-related induction and maintenance therapy for extensive-stage small cell lung cancer: a systematic review and Bayesian network meta-analysis
In brief
Two triple-drug combinations ranked highest for survival in extensive-stage small-cell lung cancer
A network analysis of 14 trials and 8,945 patients ranked atezolizumab plus lurbinectedin and chemotherapy, and benmelstobart plus anlotinib and chemotherapy, as having the greatest potential to improve survival over chemotherapy alone. These comparisons were largely indirect, and the apparent survival gains came with more toxicity; which strategy offers the best balance remains uncertain.
- Journal
- Frontiers in pharmacology (Q1)
- Published
- 15 September 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Hong-Jing Yu, Jun-Chen Liu, Dong-Sheng Zhang, Zhi Chen, Qi Deng
- PMID
- 42812321
- DOI
- 10.3389/fphar.2026.1944817
Why clinicians should know about it
- Picked for Pharmacology (medical) (top studies of the week, 4 October 2026): High-quality evidence in a top journal
Abstract
BACKGROUND: Extensive-stage small cell lung cancer (ES-SCLC) is highly aggressive with dismal prognosis, and platinum monochemotherapy offers modest long-term survival. Multiple first-line regimens integrating immunotherapy, anti-angiogenic agents and chemotherapy have been approved, yet direct head-to-head comparisons are scarce, and the optimal induction plus maintenance strategy remains undefined. In this study, a Bayesian network meta-analysis (NMA) was performed to hierarchically assess the efficacy and safety of available first-line regimens and identify balanced treatment strategies for ES-SCLC. METHODS: Eligible phase III randomized controlled trials (RCTs) were identified by searching PubMed, Embase, the Cochrane Library, and Web of Science. Trials were included if they enrolled treatment-naïve patients with ES-SCLC and reported at least one of the following outcomes: overall survival (OS), progression-free survival (PFS), or grade ≥3 treatment-related adverse events (TRAEs). NMA was implemented using the gemtc package in R. SUCRA values were calculated for treatment ranking, and subgroup analyses stratified by pharmacological mechanisms were conducted. RESULTS: Fourteen RCTs involving 8,945 patients across 18 regimens were included in the present analysis. These trials encompassed diverse combinations of mainstream immune checkpoint inhibitors, anti-angiogenic targeted agents, and chemotherapeutic agents. The atezolizumab + lurbinectedin + chemotherapy and benmelstobart + anlotinib + chemotherapy regimens showed the greatest potential for superior PFS and OS compared with chemotherapy alone. Subgroup analyses confirmed sustained efficacy benefits for PD-L1 inhibitor-based triple-combination strategies. The nivolumab + ipilimumab regimen was associated with the highest risk of severe toxicity. CONCLUSION: PD-L1 inhibitor combined with platinum-based chemotherapy together with anti-angiogenic agents or lurbinectedin conferred optimal survival benefits, yet toxicity was correspondingly augmented. This study provides valuable insights into therapeutic drug selection for ES-SCLC. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261402898, identifier 420261402898.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.