可切除非小细胞肺癌中纳武利尤单抗获益的生物标志物
Biomarkers of nivolumab benefit in resectable non-small cell lung cancer.
作者
作者单位
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA. tcascone@mdanderson.org.
- Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- McGill University Health Centre, Montreal, Quebec, Canada.
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
- Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
- University of Occupational and Environmental Health, Kitakyushu, Japan.
- Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
- Charles University, Prague, Czech Republic.
- Xiangya Hospital, Central South University, Changsha, China.
- Montpellier Regional University Hospital, Montpellier, France.
- Kanagawa Cancer Center, Yokohama, Japan.
- Hospital Israelita Albert Einstein, Sao Paulo, Brazil.
- Prof. Dr. Ion Chiricuta and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania.
- Hunan Cancer Hospital, Changsha, China.
- University Medical Center Schleswig-Holstein, Lubeck, Germany.
- Saitama Cancer Center, Saitama, Japan.
- Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- Bristol Myers Squibb, Boudry, Switzerland.
- Bristol Myers Squibb, Princeton, NJ, USA.
- Bristol Myers Squibb, Uxbridge, UK.
- Bristol Myers Squibb, Hyderabad, India.
- Hospital Universitario Puerta de Hierro, Madrid, Spain.
摘要
中文
在CheckMate 77T研究（ClinicalTrials.gov NCT04025879）中，与安慰剂相比，围手术期纳武利尤单抗显著改善了可切除非小细胞肺癌（NSCLC）患者的无事件生存期（EFS）。在随机分组后，接受纳武利尤单抗的229名患者中有98名（41%）、接受安慰剂的232名患者中有92名（41%）具有可评估的生物标志物。在98名接受纳武利尤单抗的患者中，83名（85%）在新辅助治疗开始前检测到循环肿瘤DNA（ctDNA），90名（92%）在新辅助治疗完成时检测到。在92名安慰剂治疗患者中，75名（82%）在治疗开始时检测到ctDNA，78名（85%）在完成时检测到。在98名纳武利尤单抗治疗患者中，76名（78%）在新辅助治疗前后具有可检测和可评估的ctDNA，其中50名（66%）在术前实现ctDNA清除，50名中的25名（50%）获得病理完全缓解（pCR）。安慰剂组中，92名患者中有64名（70%）在新辅助治疗前后具有可检测和可评估的ctDNA，64名中的24名（38%）术前ctDNA清除，24名中的3名（12%）获得pCR。此外，纳武利尤单抗组48名患者中有4名（8%）和安慰剂组44名患者中有9名（20%）在手术后和辅助治疗开始前为分子残留病（MRD）阴性，在辅助治疗期间转为阳性；所有患者均出现疾病复发。在KEAP1、STK11、CDKN2A和/或SMARCA4驱动基因存在单个或共突变的患者中，纳武利尤单抗（n=60）与安慰剂（n=45）相比似乎延长了EFS（风险比0.48；95%置信区间0.28-0.83）。在使用生物标志物可评估患者训练的机器学习模型中，延长EFS的首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利尤单抗治疗。这些发现为可切除NSCLC围手术期纳武利尤单抗治疗结果的预测标志物提供了见解。
English
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.
分类与指标
- 研究类型
- 临床研究
- 病种
- 肺癌
- JCR 分区
- Q1
- 影响因子
- 56.1
- 新锐分区
- 1区