新辅助化放疗联合或不联合 PD-1 抗体 sintilimab 对 pMMR 局部晚期直肠癌的疗效:随机临床试验

IF 48.8 1区 医学 Q1 CELL BIOLOGY
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引用次数: 0

摘要

新辅助化放疗(NACRT)是针对具有熟练错配修复(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和程序性细胞死亡蛋白1(PD-1)抗体sintilimab治疗。作为主要终点,对照组和实验组的总完全应答率(CR)分别为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%),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)联合评分阳性与协同效应有关。两组患者的安全性相似。在NACRT中加入PD-1抗体sintilimab可显著提高pMMR LARC的CR率,且安全性可控。PD-L1 阳性可能有助于识别从联合疗法中获益最多的患者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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

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.

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来源期刊
Cancer Cell
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.
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