Meng Yunchang, Zhang Qingfeng, Wu Ranpu, Li Huijuan, Wang Zhaofeng, Yao Yang, Li Xinjing, Chen Zhangxuan, Gong Yanzhuo, Liu Hongbing
Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing Medical University, Nanjing, China.
Department of Respiratory and Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Ther Adv Med Oncol. 2024 Oct 4;16:17588359241284929. doi: 10.1177/17588359241284929. eCollection 2024.
Neoadjuvant (NE), adjuvant (AD), and perioperative (PE) immunotherapies have gained validation in early-stage non-small cell lung cancer (NSCLC) trials. However, a comprehensive assessment of their comparative efficacy and safety is lacking.
To compare the efficacy and safety of NE, AD, and PE immunotherapies in early-stage NSCLC.
A systematic review and network meta-analysis using a Bayesian framework.
We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) of immune checkpoint inhibitors plus chemotherapy (CT) for early-stage NSCLC. Hazard ratios (HRs) and odds ratios (ORs) for binary endpoints with 95% confidence intervals (CIs) were calculated.
We included 10 RCTs involving 5569 NSCLC patients, categorized as NE, PE, or AD immunotherapy. Indirect comparisons highlighted differences in efficacy between PE and AD immunotherapy, specifically in event-free survival (EFS)/disease-free survival (DFS) (HR = 0.72, 95% CI: 0.53-0.96). NE/PE immunotherapies improved pathologic complete response (pCR) (OR = 7.56, 95% CI: 5.24-10.92), major pathologic response (MPR) (OR = 5.46, 95% CI: 3.97-7.51), and EFS (HR = 0.58, 95% CI: 0.52-0.65), while AD immunotherapy enhanced DFS (HR = 0.78, 95% CI: 0.69-0.90). Overall survival (OS) benefits were seen only with PE immunotherapy (HR = 0.66, 95% CI: 0.55-0.81). PE treatment improved EFS across various subgroups (PD-L1 < 1%, IIIB, squamous, female, without MPR/pCR, epidermal growth factor receptor (EGFR) mutant-negative), except EGFR mutant-positive NSCLC (HR = 0.54, 95% CI: 0.21-1.43). AD (OR = 1.81, 95% CI: 1.20-2.73) and PE (OR = 1.28, 95% CI: 1.10-1.50) immunotherapies were associated with higher grade ⩾3 adverse events.
In the three treatment modalities, PE immunotherapy appears to be more effective than AD immunotherapy, with PE showing significant advantages in certain subgroups that NE does not. NE and PE immunotherapy significantly improved pCR, MPR, and EFS, while AD immunotherapy significantly improved DFS in NSCLC patients compared to the control group. However, only PE immunotherapy significantly improved OS. Differences in efficacy between NE and PE across the entire population of resectable NSCLC remain to be explored in additional studies.
新辅助（NE）、辅助（AD）和围手术期（PE）免疫疗法已在早期非小细胞肺癌（NSCLC）试验中得到验证。然而，缺乏对它们的比较疗效和安全性的全面评估。
比较NE、AD和PE免疫疗法在早期NSCLC中的疗效和安全性。
使用贝叶斯框架进行系统评价和网状Meta分析。
我们在PubMed、Embase和Cochrane数据库中检索了免疫检查点抑制剂联合化疗（CT）用于早期NSCLC的随机对照试验（RCT）。计算了二元终点的风险比（HRs）和比值比（ORs）以及95%置信区间（CIs）。
我们纳入了10项RCT，涉及5569例NSCLC患者，分为NE、PE或AD免疫疗法。间接比较突出了PE和AD免疫疗法在疗效上的差异，特别是在无事件生存期（EFS）/无病生存期（DFS）方面（HR = 0.72，95% CI：0.53 - 0.96）。NE/PE免疫疗法改善了病理完全缓解（pCR）（OR = 7.56，95% CI：5.24 - 10.92）、主要病理缓解（MPR）（OR = 5.46，95% CI：3.97 - 7.51）和EFS（HR = 0.58，95% CI：0.52 - 0.65），而AD免疫疗法提高了DFS（HR = 0.78，95% CI：0.69 - 0.90）。仅PE免疫疗法显示出总生存期（OS）获益（HR = 0.66，95% CI：0.55 - 0.81）。PE治疗在各个亚组（PD-L1 < 1%、IIIB期、鳞状、女性、无MPR/pCR、表皮生长因子受体（EGFR）突变阴性）中均改善了EFS，但EGFR突变阳性的NSCLC除外（HR = 0.54，95% CI：0.21 - 1.43）。AD（OR = 1.81，95% CI：1.20 - 2.73）和PE（OR = 1.28，95% CI：1.10 - 1.50）免疫疗法与≥3级不良事件发生率较高相关。
在这三种治疗方式中，PE免疫疗法似乎比AD免疫疗法更有效，PE在某些NE不具有的亚组中显示出显著优势。与对照组相比，NE和PE免疫疗法显著改善了pCR、MPR和EFS，而AD免疫疗法显著改善了NSCLC患者的DFS。然而，只有PE免疫疗法显著改善了OS。在可切除NSCLC的整个人群中，NE和PE在疗效上的差异仍有待在更多研究中探索。
