西班牙马德里耶罗门大学医院Mariano Provencio课题组宣布他们开发出纳武单抗的生物标志物有益于可切除的非小细胞肺癌。2026年8月12日出版的《自然》发表了这项成果。

在CheckMate 77T研究（ClinicalTrials.gov NCT04025879）中，与安慰剂相比，可切除非小细胞肺癌（NSCLC）患者的围手术期nivolumab显著提高了无事件生存率（EFS）。随机化后，229例接受nivolumab治疗的患者中有98例，232例接受安慰剂治疗的患者中有92例具有可评估的生物标志物（占随机患者的41%）。在接受纳武单抗治疗的98例患者中，83例（85%）在开始新辅助治疗前检测到循环肿瘤DNA (ctDNA)， 90例（92%）在新辅助治疗结束时检测到循环肿瘤DNA。在92名接受安慰剂治疗的患者中，75名（82%）在治疗开始时检测到ctDNA， 78名（85%）在治疗结束时检测到ctDNA。在98例nivolumab治疗的患者中，76例（78%）在新辅助治疗前后有可检测和可评估的ctDNA，其中50例（66%）有术前ctDNA清除，50例（50%）中有25例有病理完全缓解（pCR）。对于安慰剂治疗组，在新辅助治疗前后，92名患者中有64名（70%）可检测和评估ctDNA， 64名患者中有24名（38%）有术前ctDNA清除，24名患者中有3名（12%）有pCR。

此外，纳武单抗组的48名患者中有4名（8%）和安慰剂组的44名患者中有9名（20%）在手术后和辅助治疗开始前分子残留病（MRD）呈阴性，在辅助治疗期间呈阳性；所有患者均有疾病复发。纳武单抗似乎延长了EFS (n=60)对照安慰剂(n=45)在KEAP1、STK11、CDKN2A和/或SMARCA4驱动基因单一或共同改变的患者中（风险比，0.48；95%可信区间，0.28-0.83）。在机器学习模型训练的主题生物标志物可评估的患者中，延长EFS的主要预测因素包括术前ctDNA清除，非n2 NSCLC， pCR，鳞状肿瘤组织学和纳武单抗治疗。这些发现为可切除NSCLC围手术期使用纳武单抗的预后预测指标提供了见解。

附：英文原文

Title: Biomarkers of nivolumab benefit in resectable non-small cell lung cancer

Author: Cascone, Tina, Awad, Mark M., Spicer, Jonathan D., He, Jie, Lu, Shun, Tanaka, Fumihiro, Cornelissen, Robin, Petruzelka, Lubos B., Gao, Yang, Pujol, Jean-Louis, Ito, Hiroyuki, de Oliveira Muniz Koch, Ludmila, Ciuleanu, Tudor-Eliade, Wu, Lin, Bohnet, Sabine, Watanabe, Yasutaka, Taube, Janis M., Deutsch, Julie Stein, Erdmann, Cinthya Coronado, Meadows-Shropshire, Stephanie, Neely, Jaclyn, Ip, Virginia, Hung, Yu-Han, Sathyanarayana, Padma, Bhatia, Sumeena, Chu, Katherine, Blum, Steven I., Lucherini, Stefano, Eddy, Nathanial, Yadav, Akshay, Provencio, Mariano

Issue&Volume: 2026-08-12

Abstract: Perioperative nivolumab significantly improved event-free survival (EFS) compared with placebo in patients with resectable non-small cell lung cancer (NSCLC) in the CheckMate 77T study (ClinicalTrials.gov NCT04025879)1. Here, after randomization, 98 out of 229 patients who received nivolumab and 92 out of 232 patients who received placebo had evaluable biomarkers (41% of randomized patients). Of the 98 patients receiving nivolumab, 83 (85%) had detectable circulating tumour DNA (ctDNA) before initiating neoadjuvant treatment and 90 (92%) at neoadjuvant treatment completion. Of the 92 placebo-treated patients, 75 (82%) had detectable ctDNA at the treatment start and 78 (85%) at completion. Among the 98 nivolumab-treated patients, 76 (78%) had detectable and evaluable ctDNA before and after neoadjuvant treatment, and 50 of them (66%) had pre-surgical ctDNA clearance, and 25 out of 50 (50%) had pathologic complete response (pCR). For the placebo-treated group, these values were 64 out 92 (70%) for detectable and evaluable ctDNA before and after neoadjuvant treatment, and 24 out of 64 (38%) had pre-surgical ctDNA clearance, and 3 out of 24 (12%) had pCR. Furthermore, 4 out of 48 (8%) patients in the nivolumab group and 9 out of 44 (20%) in the placebo group who were negative for molecular residual disease (MRD) after surgery and before adjuvant treatment initiation became positive during the adjuvant treatment period; all had disease recurrence. EFS seemed to be prolonged with nivolumab (n=60) versus placebo (n=45) in patients with single or co-alterations in any of the KEAP1, STK11, CDKN2A and/or SMARCA4 driver genes (hazard ratio, 0.48; 95% confidence interval, 0.28–0.83). In a machine-learning model trained using biomarker-evaluable patients, top predictors of prolonged EFS included pre-surgical ctDNA clearance, non-N2 NSCLC, pCR, squamous tumour histology and nivolumab treatment. These findings provide insights into predictive markers for outcomes with perioperative nivolumab in resectable NSCLC.

DOI: 10.1038/s41586-026-10925-6

Source: https://www.nature.com/articles/s41586-026-10925-6