Controversy remains as to whether pathologic complete response (pCR) and major pathologic response (MPR) represent surrogate end points for event-free survival (EFS) and overall survival (OS) in neoadjuvant trials for resectable NSCLC. A search of PubMed and archives of international conference abstracts was performed from June 2017 through October 31, 2023. Studies incorporating a neoadjuvant arm with immune checkpoint blockade alone or in combination with chemotherapy were included. Those not providing information regarding pCR, MPR, EFS, or OS were excluded. For trial-level surrogacy, log ORs for pCR and MPR and log hazard ratios for EFS and OS were analyzed using a linear regression model weighted by sample size. The regression coefficient and with 95% confidence interval were calculated by the bootstrapping approach. Seven randomized clinical trials were identified for a total of 2385 patients. At the patient level, the of pCR and MPR with 2-year EFS were 0.82 (0.66–0.94) and 0.81 (0.63–0.93), respectively. The OR of 2-year EFS rates by response status was 0.12 (0.07–0.19) and 0.11 (0.05–0.22), respectively. For the 2-year OS, the of pCR and MPR were 0.55 (0.09–0.98) and 0.52 (0.10–0.96), respectively. At the trial level, the for the association of OR for response and HR for EFS was 0.58 (0.00–0.97) and 0.61 (0.00–0.97), respectively. Our analyses reveal a robust correlation between pCR and MPR with 2-year EFS but not OS. Trial-level surrogacy was moderate but imprecise. More mature follow-up and data to assess the impact of study crossover are needed.

中文翻译：

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在可切除非小细胞肺癌新辅助免疫检查点阻断随机对照试验中评估主要病理缓解和病理完全缓解作为生存替代终点

关于病理完全缓解 (pCR) 和主要病理缓解 (MPR) 是否代表可切除 NSCLC 新辅助试验中无事件生存 (EFS) 和总生存 (OS) 的替代终点，仍存在争议。 2017 年 6 月至 2023 年 10 月 31 日期间对 PubMed 和国际会议摘要档案进行了检索。纳入了新辅助治疗单独或与化疗联合免疫检查点阻断的研究。那些不提供有关 pCR、MPR、EFS 或 OS 信息的人被排除在外。对于试验级代孕，使用按样本量加权的线性回归模型分析了 pCR 和 MPR 的对数 OR 以及 EFS 和 OS 的对数风险比。通过 bootstrapping 方法计算回归系数和 95% 置信区间。共确定了 7 项随机临床试验，涉及 2385 名患者。在患者层面，2 年 EFS 的 pCR 和 MPR 分别为 0.82 (0.66–0.94) 和 0.81 (0.63–0.93)。按缓解状态划分的 2 年 EFS 率的 OR 分别为 0.12 (0.07–0.19) 和 0.11 (0.05–0.22)。对于 2 年 OS，pCR 和 MPR 分别为 0.55 (0.09–0.98) 和 0.52 (0.10–0.96)。在试验层面，缓解的 OR 和 EFS 的 HR 的关联度分别为 0.58 (0.00–0.97) 和 0.61 (0.00–0.97)。我们的分析揭示了 pCR 和 MPR 与 2 年 EFS 之间存在很强的相关性，但与 OS 没有相关性。试验级代孕适度但不精确。需要更成熟的后续行动和数据来评估研究交叉的影响。