Gemelli Maria, Cortinovis Diego, Carola Giorgia, Moretti Laura, Piazza Francesca, Calza Stefano, Ricotta Riccardo, Grisanti Salvatore, Rota Matteo
Medical Oncology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica, 20099 Milan, Italy.
Division of Medical Oncology, Fondazione IRCCS San Gerardo dei Tintori, Via GB Pergolesi 33, 20900 Monza, Italy; School of Medicine and Surgery, University of Milano Bicocca, 20126 Milan, Italy.
Lung Cancer. 2025 Jul;205:108621. doi: 10.1016/j.lungcan.2025.108621. Epub 2025 Jun 10.
despite advancements in NSCLC treatment, PD-L1 negative patients remain a therapeutic challenge. This meta-analysis evaluates the efficacy of immune checkpoint inhibitors (ICIs) and their combinations in PD-L1 negative NSCLC.
Major databases (PubMed, Embase, Cochrane Library) were searched using terms such as "PD-L1 negative," "NSCLC," "chemotherapy," and "immunotherapy." Phase I-III clinical trials comparing ICIs-based treatments in PD-L1 negative NSCLC were included, excluding non-peer-reviewed studies. Data extraction followed PRISMA guidelines, with independent review by two researchers. Random-effects models were used to pool data, assessing overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).
This analysis included 43 trials with 7039 patients. Immunotherapy alone yielded an ORR of 11 %, while immunotherapy combined with chemotherapy achieved the highest ORR (48 %). Combination immunotherapy alone and chemotherapy alone showed comparable ORRs (23 % vs. 22 %). Median PFS was 2.3 months for immunotherapy alone, 6.8 months for immunotherapy plus chemotherapy, and 5.7 months for combo immunotherapy. OS was 10.1 months for immunotherapy alone, 15.6 months for immunotherapy plus chemotherapy, and 17.6 months for combo immunotherapy. Network meta-analysis highlighted pembrolizumab with platinum-based chemotherapy as the most effective, achieving the highest ORR and a 45 % PFS improvement compared to chemotherapy alone.
Combination therapies, particularly ICIs with chemotherapy, significantly improve ORR, PFS, and OS in PD-L1 negative NSCLC, underscoring their potential as optimal strategies for this population.
尽管非小细胞肺癌（NSCLC）治疗取得了进展，但程序性死亡配体1（PD-L1）阴性患者仍然是一个治疗挑战。本荟萃分析评估了免疫检查点抑制剂（ICI）及其联合用药在PD-L1阴性NSCLC中的疗效。
使用“PD-L1阴性”“NSCLC”“化疗”和“免疫疗法”等术语检索主要数据库（PubMed、Embase、Cochrane图书馆）。纳入比较PD-L1阴性NSCLC中基于ICI治疗的I-III期临床试验，排除未经同行评审的研究。数据提取遵循系统评价和Meta分析的首选报告项目（PRISMA）指南，由两名研究人员独立审核。采用随机效应模型汇总数据，评估总生存期（OS）、无进展生存期（PFS）和客观缓解率（ORR）。
该分析纳入了43项试验，共7039例患者。单纯免疫疗法的ORR为11%，而免疫疗法联合化疗的ORR最高（48%）。单纯联合免疫疗法和单纯化疗的ORR相当（23%对22%）。单纯免疫疗法的中位PFS为2.3个月，免疫疗法加化疗为6.8个月，联合免疫疗法为5.7个月。单纯免疫疗法的OS为10.1个月，免疫疗法加化疗为15.6个月，联合免疫疗法为17.6个月。网状Meta分析强调帕博利珠单抗联合铂类化疗是最有效的，与单纯化疗相比，ORR最高，PFS提高了45%。
联合治疗，尤其是ICI与化疗联合，可显著改善PD-L1阴性NSCLC患者的ORR、PFS和OS，凸显了其作为该人群最佳治疗策略的潜力。
