Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial,Cancer Cell

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Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial
Cancer Cell ( IF 48.8 ) Pub Date : 2024-08-01 , DOI: 10.1016/j.ccell.2024.07.004
Wei-Wei Xiao ₁ , Gong Chen ₂ , Yuan-Hong Gao ₃ , Jun-Zhong Lin ₂ , Xiao-Jun Wu ₂ , Hui-Long Luo ₃ , Zhen-Hai Lu ₂ , Qiao-Xuan Wang ₃ , Rui Sun ₃ , Pei-Qiang Cai ₄ , Chong-Mei Zhu ₅ , Min Liu ₆ , Ji-Bin Li ₇ , Yi-Rui Wang ₃ , Ying Jin ₈ , Feng Wang ₈ , Hai-Tao Luo ₉ , Cai-Ling Li ₉ , Zhi-Zhong Pan ₂ , Rui-Hua Xu ₈

Affiliation

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China; United Laboratory of Frontier Radiotherapy Technology of Sun Yat-sen University & Chinese Academy of Sciences Ion Medical Technology Co., Ltd, Guangzhou, China.
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.
Department of Radiation Oncology, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.
Department of Radiology, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.
Department of Pathology, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.
Department of Ultrasound, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.
Department of Statistics, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.
Department of Medical Oncology, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, China.
Shenzhen Engineering Center for Translational Medicine of Precision Cancer Immunodiagnosis and Therapy, YuceBio Technology Co., Ltd, Shenzhen, China.

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.

中文翻译：

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

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 阳性可能有助于确定哪些患者可能从联合治疗中获益最多。

更新日期：2024-08-01

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