Portsmouth Hospitals University NHS Trust, Portsmouth, United Kingdom.
Faculty of Science and Health, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, United Kingdom.
JAMA Netw Open. 2024 Apr 1;7(4):e246837. doi: 10.1001/jamanetworkopen.2024.6837.
Randomized clinical trials (RCTs) with neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy (ICI-chemotherapy) for patients with early-stage non-small cell lung cancer (NSCLC) have reported consistent associations with event-free survival (EFS) and pathologic complete response (pCR) pending longer follow-up for overall survival data.
To assess the pooled benefit of ICI-chemotherapy in 2-year EFS and pCR among patients with NSCLC and examine the impact of clinical, pathologic, and treatment-related factors.
Full-text articles and abstracts in English were searched in EMBASE, PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews through November 1, 2023, and in oncology conference proceedings from January 1, 2008, to November 1, 2023.
Phase 2 or 3 RCTs with neoadjuvant ICI-chemotherapy with or without adjuvant ICIs vs neoadjuvant chemotherapy alone with or without placebo or observation in patients with previously untreated NSCLC staged IB to IIIB were included.
Data extraction of prespecified data elements was performed by 2 reviewers using a structured data abstraction electronic form. A random-effects model was used for meta-analysis. The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline.
Two-year EFS and pCR were the outcomes of interest in patients who received neoadjuvant ICI-chemotherapy (experimental arm) or neoadjuvant chemotherapy alone (control arm). Aggregated pooled hazard ratios (HRs) for time-to-event outcomes (2-year EFS) and risk ratios (RRs) for dichotomous outcomes (pCR) with their respective 95% CIs were calculated.
Eight trials with 3387 patients were included, with some concerns of risk of bias as assessed by the Cochrane Collaboration method, mainly related to outcomes measurements. Neoadjuvant ICI-chemotherapy was associated with improved 2-year EFS (HR, 0.57; 95% CI, 0.50-0.66; P < .001) and increased pCR rate (RR, 5.58; 95% CI, 4.27-7.29; P < .001) in the experimental vs control treatment arms. This association was not significantly modified by the main patient characteristics; tumor- or treatment-related factors, including tumor programmed cell death ligand 1 (PD-L1) status; type of platinum-compound chemotherapy; number of cycles of neoadjuvant ICI-chemotherapy; or addition of adjuvant ICIs. Patients whose tumor cells were negative for PD-L1 were at higher risk of relapse (HR, 0.75; 95% CI, 0.62-0.91) than were those with low (HR, 0.61; 95% CI, 0.37-0.71) or high PD-L1 (HR, 0.40; 95% CI, 0.27-0.58) (P = .005).
In this systematic review and meta-analysis of neoadjuvant ICI-chemotherapy RCTs in patients with early-stage NSCLC, 3 cycles of neoadjuvant platinum-based ICI-chemotherapy were associated with a meaningful improvement in 2-year EFS and pCR.
针对早期非小细胞肺癌（NSCLC）患者的新辅助免疫检查点抑制剂（ICI）联合化疗的随机临床试验（RCT）报告了与无事件生存（EFS）和病理完全缓解（pCR）的一致关联，等待更长时间以获得总生存数据。
评估 NSCLC 患者新辅助 ICI-化疗在 2 年 EFS 和 pCR 方面的总体获益，并研究临床、病理和治疗相关因素的影响。
通过 2023 年 11 月 1 日在 EMBASE、PubMed、Cochrane 对照试验中心注册库和 Cochrane 系统评价数据库中的全文文章和摘要，以及 2008 年 1 月 1 日至 2023 年 11 月 1 日肿瘤学会议论文集进行检索。
纳入了新辅助 ICI-化疗联合或不联合新辅助化疗加安慰剂或观察组治疗、未经治疗的 NSCLC 分期 IB 至 IIIB 患者的 2 期或 3 期 RCT。
使用结构化数据提取电子表格由 2 位审阅者对预设数据元素进行数据提取。使用随机效应模型进行荟萃分析。荟萃分析遵循系统评价和荟萃分析的首选报告项目指南。
接受新辅助 ICI-化疗（实验组）或新辅助化疗单独治疗（对照组）的患者的主要结局是 2 年 EFS 和 pCR。计算了时间事件结局（2 年 EFS）的聚合汇总风险比（HR）和二项结局（pCR）的风险比（RR）及其各自的 95%置信区间（CI）。
纳入了 8 项试验，共 3387 名患者，其中一些与结局测量相关的偏倚风险评估被认为存在担忧，主要是由于偏倚风险评估。与对照组相比，新辅助 ICI-化疗与改善的 2 年 EFS（HR，0.57；95%CI，0.50-0.66；P<0.001）和增加的 pCR 率（RR，5.58；95%CI，4.27-7.29；P<0.001）相关。这种关联不受主要患者特征的显著影响；肿瘤或治疗相关因素，包括肿瘤程序性细胞死亡配体 1（PD-L1）状态；铂类化疗药物的类型；新辅助 ICI-化疗的周期数；或添加辅助 ICI。PD-L1 阴性肿瘤细胞的患者复发风险较高（HR，0.75；95%CI，0.62-0.91），而低（HR，0.61；95%CI，0.37-0.71）或高 PD-L1（HR，0.40；95%CI，0.27-0.58）（P=0.005）。
在这项对新辅助 ICI-化疗治疗早期 NSCLC 的 RCT 的系统评价和荟萃分析中，3 个周期的新辅助基于铂的 ICI-化疗与 2 年 EFS 和 pCR 的显著改善相关。
