新辅助放化疗联合或不联合 PD-1 抗体信迪利单抗对 pMMR 局部晚期直肠癌的影响：一项随机临床试验。
Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial.
发表日期：2024 Jul 24
作者：
Wei-Wei Xiao, Gong Chen, Yuan-Hong Gao, Jun-Zhong Lin, Xiao-Jun Wu, Hui-Long Luo, Zhen-Hai Lu, Qiao-Xuan Wang, Rui Sun, Pei-Qiang Cai, Chong-Mei Zhu, Min Liu, Ji-Bin Li, Yi-Rui Wang, Ying Jin, Feng Wang, Hai-Tao Luo, Cai-Ling Li, Zhi-Zhong Pan, Rui-Hua Xu
来源：
CANCER CELL
摘要：
新辅助放化疗 (NACRT) 是具有良好错配修复 (pMMR) 蛋白的局部晚期直肠癌 (LARC) 患者的标准治疗方法。在这项随机 2 期试验 (ClinicalTrial.gov: NCT04304209) 中，134 名 pMMR LARC 患者被随机 (1:1) 分配接受 NACRT 或 NACRT 联合程序性细胞死亡蛋白 1 (PD-1) 抗体信迪利单抗治疗。作为主要终点，总完全缓解 (CR) 率为 26.9%（18/67，95% 置信区间 [CI] 16.0%-37.8%）和 44.8%（30/67，95% CI 32.6%-57.0%） ）分别在对照组和实验组中具有显着差异（卡方检验 p = 0.031）。响应比为 1.667 (95% CI 1.035-2.683)。免疫组织化学显示PD-1配体1（PD-L1）联合阳性评分与协同效应相关。两臂之间的安全性相似。将 PD-1 抗体信迪利单抗添加到 NACRT 中可显着提高 pMMR LARC 的 CR 率，且安全性可控。 PD-L1 阳性可能有助于识别可能从联合治疗中获益最多的患者。版权所有 © 2024 Elsevier Inc. 保留所有权利。
Neoadjuvant chemoradiotherapy (NACRT) was the standard treatment for patients with locally advanced rectal cancer (LARC) with proficient mismatch repair (pMMR) proteins. In this randomized phase 2 trial (ClinicalTrial.gov: NCT04304209), 134 pMMR LARC patients were randomly (1:1) assigned to receive NACRT or NACRT and the programmed cell death protein 1 (PD-1) antibody sintilimab. As the primary endpoint, the total complete response (CR) rate is 26.9% (18/67, 95% confidence interval [CI] 16.0%-37.8%) and 44.8% (30/67, 95% CI 32.6%-57.0%) in the control and experimental arm, respectively, with significant difference (p = 0.031 for chi-squared test). Response ratio is 1.667 (95% CI 1.035-2.683). Immunohistochemistry shows PD-1 ligand 1 (PD-L1) combined positive score is associated with the synergistic effect. The safety profile is similar between the arms. Adding the PD-1 antibody sintilimab to NACRT significantly increases the CR rate in pMMR LARC, with a manageable safety profile. PD-L1 positivity may help identify patients who might benefit most from the combination therapy.Copyright © 2024 Elsevier Inc. All rights reserved.