Liu Na, Zhang Baowanze, He Jiali, Li Su
Department of Pharmacy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, China.
Front Immunol. 2025 Sep 16;16:1635757. doi: 10.3389/fimmu.2025.1635757. eCollection 2025.
Significant efficacy heterogeneity exists between first- and second-line immunotherapy regimens for advanced squamous non-small cell lung cancer (SqNSCLC), but most regimens lack directly comparable clinical trial evidence, resulting in unclear prioritization. This analysis identifies optimal treatment strategies by evaluating differences in efficacy across immune checkpoint inhibitors (ICIs).
We search through comprehensive databases, including PubMed, Embase, the Cochrane Library and the Clinical Trials Database. Traditional meta-analysis was done using Stata 15.0, while Bayesian-framework network meta-analysis was implemented with R's GEMTC package via Markov chain Monte Carlo simulation. Subgroup analyses were performed for different PD-L1 expression levels, number of treatments, ethnic groups, and smoking history.
We included 25 randomized controlled trials. Immune-related therapy can provide significant benefit relative to chemotherapy alone in advanced SqNSCLC. Compared with chemotherapy, except for ipilimumab+chemo [HR = 0.92,95%CI: (0.59-1.40)], atezolizumab+chemo [HR = 0.88, 95%CI: (0.56-1.40)], and durvalumab+chemo [HR = 0.84, 95% CI: (0.52-1.40)], durvalumab+ tremelimumab+chemo [HR = 0. 88, 95% CI: (0.54-1.40)], which significantly improved overall survival(OS). Cemiplimab [HR = 0.48, 95% CI: (0.34-0.67)] showed the best OS benefit. Compared with chemotherapy, all immunotherapies significantly improved progression-free survival (PFS) except for ipilimumab+chemo [HR = 0.87, 95% CI: (0.75-1.00)]. Sugemalimab+chemo provided the best survival benefit [HR = 0.34, 95% CI: (0.24-0.48)]. For PD-L1≥50% tumors, penpulimab showed excellent OS and PFS; for PD-L1 1-49% tumors, pembrolizumab+chemo and camrelizumab+chemo achieved the best OS and PFS, respectively; for PD-L1≥1% tumors, the tislelizumab+chemo and camrelizumab+chemo showed the best OS and PFS results, while for tumors with PD-L1 <1%, both nivolumab and serplulimab+chemo provided significant survival benefit. In Asian patients, patients treated with pembrolizumab or pembrolizumab + chemotherapy had favorable OS and PFS benefits. In non-Asian patients, there was also favorable OS and PFS benefit with cemiplimab. For former/current smokers, pembrolizumab+chemotherapy and camrelizumab+chemotherapy had significant OS and PFS benefit, but most immunotherapies did not improve OS and PFS in never smokers. Camrelizumab+chemo [OR = 3.5, 95% CI: (2.3-5.3)] had the best overall response rate (ORR) benefit. Ipilimumab+chemo had the highest incidence of adverse events (AEs) [OR = 2.0, 95% CI:(1.5-2.7)].
https://www.crd.york.ac.uk/prospero/, identifier CRD420251027447.
晚期鳞状非小细胞肺癌（SqNSCLC）一线和二线免疫治疗方案之间存在显著的疗效异质性，但大多数方案缺乏直接可比的临床试验证据，导致治疗方案的优先排序不明确。本分析通过评估免疫检查点抑制剂（ICI）之间的疗效差异来确定最佳治疗策略。
我们检索了包括PubMed、Embase、Cochrane图书馆和临床试验数据库在内的综合数据库。使用Stata 15.0进行传统荟萃分析，同时通过R的GEMTC包，采用马尔可夫链蒙特卡罗模拟进行贝叶斯框架网络荟萃分析。对不同的PD-L1表达水平、治疗次数、种族和吸烟史进行亚组分析。
我们纳入了25项随机对照试验。免疫相关治疗相对于单纯化疗可在晚期SqNSCLC中提供显著益处。与化疗相比，除了伊匹木单抗+化疗[HR = 0.92，95%CI：（0.59-1.40）]、阿替利珠单抗+化疗[HR = 0.88，95%CI：（0.56-1.40）]、度伐利尤单抗+化疗[HR = 0.84，95%CI：（0.52-1.40）]、度伐利尤单抗+曲美木单抗+化疗[HR = 0.88，95%CI：（0.54-1.40）]外，其他方案均显著改善了总生存期（OS）。西米普利单抗[HR = 0.48，95%CI：（0.34-0.67）]显示出最佳的OS获益。与化疗相比，除伊匹木单抗+化疗[HR = 0.87，95%CI：（0.75-1.00）]外，所有免疫治疗均显著改善了无进展生存期（PFS）。苏金单抗+化疗提供了最佳的生存获益[HR = 0.34，95%CI：（0.24-0.48）]。对于PD-L1≥50%的肿瘤，派安普利单抗显示出优异的OS和PFS；对于PD-L1 1-49%的肿瘤，帕博利珠单抗+化疗和卡瑞利珠单抗+化疗分别取得了最佳的OS和PFS；对于PD-L1≥1%的肿瘤，替雷利珠单抗+化疗和卡瑞利珠单抗+化疗显示出最佳的OS和PFS结果，而对于PD-L1<1%的肿瘤，纳武利尤单抗和塞瑞普利单抗+化疗均提供了显著的生存获益。在亚洲患者中，接受帕博利珠单抗或帕博利珠单抗+化疗治疗的患者具有良好的OS和PFS获益。在非亚洲患者中，西米普利单抗也具有良好的OS和PFS获益。对于曾经/现在吸烟者，帕博利珠单抗+化疗和卡瑞利珠单抗+化疗具有显著的OS和PFS获益，但大多数免疫治疗在从不吸烟者中并未改善OS和PFS。卡瑞利珠单抗+化疗[OR = 3.5，95%CI：（2.3-5.3）]具有最佳的总缓解率（ORR）获益。伊匹木单抗+化疗的不良事件（AE）发生率最高[OR = 2.0，95%CI：（1.5-2.7）]。
