A prospective study of neoadjuvant pembrolizumab plus chemotherapy for resectable esophageal squamous cell carcinoma: The Keystone-001 trial

IF 48.8 1区医学 Q1 CELL BIOLOGY

Cancer Cell Pub Date : 2024-10-14 DOI:10.1016/j.ccell.2024.09.008

Xiaobin Shang, Yongjie Xie, Jinpu Yu, Chen Zhang, Gang Zhao, Fei Liang, Liang Liu, Weihong Zhang, Runmei Li, Wenwen Yu, Jie Yue, Chuangui Chen, Xiaofeng Duan, Zhao Ma, Zuoyu Chen, Yanjuan Xiong, Fan Yang, Jianyu Xiao, Rui Zhang, Pengpeng Liu, Hongjing Jiang

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引用次数: 0

Abstract

In this phase II study, 47 patients with locally advanced, resectable esophageal squamous cell carcinoma (ESCC) received three cycles of pembrolizumab plus chemotherapy, followed by Da Vinci robot-assisted surgery. The primary endpoints were safety and major pathological response (MPR). Key secondary endpoints included complete pathological response (pCR) and survival. No grade ≥3 adverse events or surgical delays occurred during neoadjuvant therapy. Among 46 patients studied for efficacy, the MPR and pCR rates were 72% and 41%, respectively. After a median follow-up of 27.2 months, the 2-year overall survival (OS) and disease-free survival (DFS) rates were 91% and 89%, respectively. Expansion of TRGC2⁺ NKT cells in peripheral blood correlated with neoadjuvant treatment effectiveness, which was validated by in vitro organoid experiments and external cancer datasets, and its functional classification and mechanism of action were further explored. These findings show preoperative pembrolizumab plus chemotherapy is a promising therapeutic strategy for resectable ESCC.

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针对可切除食管鳞状细胞癌的新辅助 pembrolizumab 加化疗的前瞻性研究：Keystone-001 试验

在这项II期研究中，47名局部晚期、可切除食管鳞状细胞癌（ESCC）患者接受了三个周期的pembrolizumab+化疗，随后接受达芬奇机器人辅助手术。主要终点是安全性和主要病理反应（MPR）。主要次要终点包括完全病理反应（pCR）和生存期。新辅助治疗期间未发生≥3级不良事件或手术延迟。在接受疗效研究的46名患者中，MPR和pCR率分别为72%和41%。中位随访 27.2 个月后，2 年总生存率（OS）和无病生存率（DFS）分别为 91% 和 89%。外周血中TRGC2+ NKT细胞的扩增与新辅助治疗效果相关，这一点已通过体外类器官实验和外部癌症数据集得到验证，其功能分类和作用机制也得到了进一步探讨。这些研究结果表明，术前使用pembrolizumab加化疗是一种治疗可切除ESCC的有效策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Cell 医学-肿瘤学

CiteScore

55.20

自引率

1.20%

发文量

179

审稿时长

4-8 weeks

期刊介绍： Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows: Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers. Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice. Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers. Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies. Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.