中山大学徐瑞华团队揭示新辅助化疗放疗联合或不联合PD-1抗体sintilimab在pMMR局部晚期直肠癌中的效果。2024年8月1日，国际知名学术期刊《癌细胞》在线发表了这一成果。

研究人员表示，新辅助化疗放疗（NACRT）是针对局部晚期直肠癌（LARC）伴有有效错配修复（pMMR）蛋白患者的标准治疗方案。

在一项随机2期临床试验（ClinicalTrial.gov: NCT04304209）中，134名pMMR LARC患者被随机（1:1）分配接受NACRT或NACRT加程序性细胞死亡蛋白1（PD-1）抗体sintilimab治疗。

主要终点为完全缓解（CR）总率，在对照组和实验组分别为26.9%（67例中的18例，95%置信区间[CI] 16.0%–37.8%）和44.8%（67例中的30例，95% CI 32.6%–57.0%），差异显著（卡方检验p=0.031）。反应比为1.667（95% CI 1.035–2.683）。

免疫组化显示，PD-1配体1（PD-L1）联合阳性评分与协同效应相关。两组的安全性档案相似。将PD-1抗体sintilimab加入NACRT治疗显著提高了pMMR LARC患者的CR率，并且安全性可控。PD-L1阳性可能有助于识别从联合治疗中获益最大的患者。

附：英文原文

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

Author: 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

Issue&Volume: 2024-08-01

Abstract: Neoadjuvant chemoradiotherapy (NACRT) was the standard treatment for patients withlocally advanced rectal cancer (LARC) with proficient mismatch repair (pMMR) proteins.In this randomized phase 2 trial (ClinicalTrial.gov: NCT04304209), 134 pMMR LARC patientswere randomly (1:1) assigned to receive NACRT or NACRT and the programmed cell deathprotein 1 (PD-1) antibody sintilimab. As the primary endpoint, the total completeresponse (CR) rate is 26.9% (18/67, 95% confidence interval [CI] 16.0%–37.8%) and44.8% (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). Immunohistochemistryshows PD-1 ligand 1 (PD-L1) combined positive score is associated with the synergisticeffect. The safety profile is similar between the arms. Adding the PD-1 antibody sintilimabto NACRT significantly increases the CR rate in pMMR LARC, with a manageable safetyprofile. PD-L1 positivity may help identify patients who might benefit most from thecombination therapy.

DOI: 10.1016/j.ccell.2024.07.004

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(24)00269-1