Zhang Chao, Sun Yu-Xuan, Yi Ding-Cheng, Jiang Ben-Yuan, Yan Li-Xu, Liu Ze-Dao, Peng Li-Shan, Zhang Wen-Jie, Sun Hao, Chen Zhi-Yong, Wang Dan-Hua, Peng Di, Chen Song-An, Li Si-Qi, Zhang Ze, Tan Xiao-Yue, Yang Jie, Zhao Zhang-Yi, Zhang Wan-Ting, Su Jian, Li Yang-Si, Liao Ri-Qiang, Dong Song, Xu Chong-Rui, Zhou Qing, Yang Xue-Ning, Wu Yi-Long, Zhang Ze-Min, Zhong Wen-Zhao
Department of Pulmonary Surgery, Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China; Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China; School of Medicine, South China University of Technology, Guangzhou, China.
School of Life Sciences, Peking University, Beijing, China.
Cell Rep Med. 2024 Jul 16;5(7):101615. doi: 10.1016/j.xcrm.2024.101615. Epub 2024 Jun 18.
The clinical efficacy of neoadjuvant immunotherapy plus chemotherapy remains elusive in localized epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Here, we report interim results of a Simon's two-stage design, phase 2 trial using neoadjuvant sintilimab with carboplatin and nab-paclitaxel in resectable EGFR-mutant NSCLC. All 18 patients undergo radical surgery, with one patient experiencing surgery delay. Fourteen patients exhibit confirmed radiological response, with 44% achieving major pathological response (MPR) and no pathological complete response (pCR). Similar genomic alterations are observed before and after treatment without influencing the efficacy of subsequent EGFR-tyrosine kinase inhibitors (TKIs) in vitro. Infiltration and T cell receptor (TCR) clonal expansion of CCR8 regulatory T (Treg)/CXCL13 exhausted T (Tex) cells define a subtype of EGFR-mutant NSCLC highly resistant to immunotherapy, with the phenotype potentially serving as a promising signature to predict immunotherapy efficacy. Informed circulating tumor DNA (ctDNA) detection in EGFR-mutant NSCLC could help identify patients nonresponsive to neoadjuvant immunochemotherapy. These findings provide supportive data for the utilization of neoadjuvant immunochemotherapy and insight into immune resistance in EGFR-mutant NSCLC.
新辅助免疫疗法联合化疗在局部表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）中的临床疗效仍不明确。在此，我们报告了一项采用新辅助信迪利单抗联合卡铂和白蛋白结合型紫杉醇治疗可切除EGFR突变NSCLC的Simon两阶段设计2期试验的中期结果。所有18例患者均接受了根治性手术，其中1例患者手术延迟。14例患者表现出影像学确认的反应，44%达到主要病理缓解（MPR），无病理完全缓解（pCR）。治疗前后观察到相似的基因组改变，且不影响后续EGFR酪氨酸激酶抑制剂（TKIs）的体外疗效。CCR8调节性T（Treg）/CXCL13耗竭性T（Tex）细胞的浸润和T细胞受体（TCR）克隆扩增定义了一种对免疫疗法高度耐药的EGFR突变NSCLC亚型，该表型可能作为预测免疫疗法疗效的有前景的标志物。在EGFR突变NSCLC中进行有创循环肿瘤DNA（ctDNA）检测有助于识别对新辅助免疫化疗无反应的患者。这些发现为新辅助免疫化疗的应用提供了支持性数据，并深入了解了EGFR突变NSCLC中的免疫耐药性。
