Efficacy and safety of personalized optimal PD-(L)1 combinations in advanced NSCLC: a network meta-analysis

作者：Chu X, Tian W, Ning J, Zhou R · 发表于：Journal of the National Cancer Institute · 年份：2024 · DOI：10.1093/jnci/djae137 · 研究领域：B7-H1 Antigen、Carcinoma, Non-Small-Cell Lung、Immune Checkpoint Inhibitors、Lung Neoplasms、Humans、Antineoplastic Combined Chemotherapy Protocols、Clinical Trials, Phase II as Topic、Clinical Trials, Phase III as Topic、CTLA-4 Antigen、Immunotherapy、Precision Medicine、Progression-Free Survival

INTRODUCTION: Programmed death 1 (PD-1)/programmed death 1 ligand 1 (PD-L1)-directed immunotherapy has revolutionized the treatments for advanced non-small cell lung cancer (NSCLC), whereas the optimal therapeutic combinations remain uncertain. METHODS: Our study encompassed phase II/III randomized controlled trials (RCTs) that involved anti-PD-(L)1-based therapies for stage-IV NSCLC. The primary outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and incidences of adverse events. Subgroup analyses were conducted by treatment lines, PD-L1 expression levels, histological types, and metastatic sites. RESULTS: Our analysis incorporated 38 publications, covering 14 therapeutic combinations and involving 18 048 participants. PD-(L)1+chemotherapy (CT), PD-(L)1+ cytotoxic T lymphocyte-associated antigen-4 (CTLA4) +CT, and PD-(L)1+ T-cell immunoglobulin and ITIM domain were notably effective in prolonging OS. Overall, PD-(L)1+CT and PD-(L)1+CT+ vascular endothelial growth factor (VEGF) were significantly beneficial for PFS and ORR. As for the subsequent-line treatments, incorporating radiotherapy can enhance PFS and ORR (ranked fourth among enrolled treatments). For patients with PD-L1 <1%, PD-(L)1+CT+VEGF and PD-(L)1+CTLA4+CT were favorable approaches. Conversely, in patients with PD-L1 ≥50%, PD-(L)1+CT represented an effective treatment. Patients with nonsquamous cell carcinoma or liver metastases might benefit from the additio...