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.
Cancer Cell. 2024 Sep 9;42(9):1570-1581.e4. doi: 10.1016/j.ccell.2024.07.004. Epub 2024 Aug 1.
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.
新辅助放化疗（NACRT）是具有高错配修复（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 期临床试验（ClinicalTrials.gov：NCT04304209）中，134 例 pMMR LARC 患者被随机（1:1）分配接受 NACRT 或 NACRT 联合程序性死亡蛋白 1（PD-1）抗体信迪利单抗治疗。主要终点是总完全缓解（CR）率，对照组为 26.9%（18/67，95%置信区间[CI]为 16.0%-37.8%），实验组为 44.8%（30/67，95%CI 为 32.6%-57.0%），差异有统计学意义（卡方检验，p=0.031）。反应比为 1.667（95%CI 为 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。两组的安全性特征相似。在 NACRT 中加入 PD-1 抗体信迪利单抗可显著提高 pMMR LARC 的 CR 率，且安全性可管理。PD-L1 阳性可能有助于确定最有可能从联合治疗中获益的患者。
N Engl J Med. 2022-6-23
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