Short-course-based TNT with or without PD-1 inhibitor for pMMR locally advanced rectal cancer: Phase 2 results of a randomized trial (STELLAR II).

IF 11.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Med Pub Date : 2025-08-21 DOI:10.1016/j.medj.2025.100807

Yuan Tang, Hao-Yue Li, Li-Chun Wei, Ning Li, Wen-Jue Zhang, Yu-Fei Lu, Fei-Yan Deng, Tong-Zhen Xu, Jia-Cheng Shuai, Zi-Fa Lei, Xian-Yu Meng, Shu-Nan Qi, Yong-Wen Song, Wen-Wen Zhang, Hao Jing, Gong Li, Shi-Xin Liu, Ying-Jie Wang, Zheng Liu, Hui-Ying Ma, Ning-Yu Wang, Bo Chen, Shu-Lian Wang, Ye-Xiong Li, Li-Na Zhao, Jian-Qiang Tang, Zheng Jiang, Ying-Gang Chen, Hai-Tao Zhou, Chen Hu, Jing Jin

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引用次数: 0

Abstract

Background: The therapeutic efficacy and mode of combining immunotherapy with neoadjuvant chemoradiotherapy in proficient mismatch repair (pMMR)/microsatellite stable (MSS) locally advanced rectal cancer (LARC) remain uncertain.

Methods: In this multicenter, randomized, seamless phase 2/3 trial (ClinicalTrials.gov: NCT05484024), eligible participants were randomly assigned (1:1) to receive short-course radiotherapy (SCRT) (5 Gy × 5), followed by 4 cycles of capecitabine and oxaliplatin or 6 cycles of leucovorin, oxaliplatin, and fluorouracil, with (iTNT group) or without (total neoadjuvant therapy [TNT] group) 4 cycles of sintilimab. Following neoadjuvant therapy, participants underwent surgery or a watch-and-wait strategy based on clinical complete response. The primary endpoints were the complete response (CR) rate for phase 2 and the 3-year disease-free survival (DFS) rate for phase 3.

Findings: 218 patients were randomized to the iTNT group (n = 110) and the TNT group (n = 108). All patients completed SCRT, with 88.2% in the iTNT group and 93.5% in the TNT group completing 4 cycles of neoadjuvant treatment. The CR rate was significantly higher in the iTNT group (45.5% vs. 25.0%; p = 0.003). Grade 3-4 treatment-related adverse events were reported in 34.5% of the iTNT group and 19.4% of the TNT group (p = 0.012), with thrombocytopenia, diarrhea, leukopenia, and neutropenia being the most frequently observed. Grade 3-4 immune-related adverse events occurred in 5.5% of patients in the iTNT group.

Conclusions: The addition of the PD-1 inhibitor sintilimab significantly enhances the CR rate compared to SCRT-based TNT, with favorable tolerability in patients with pMMR/MSS LARC.

Funding: This work was funded by the National Natural Science Foundation of China (82473248) and the Shenzhen Medical Research Fund (C2301001).

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短期疗程TNT联合或不联合PD-1抑制剂治疗pMMR局部晚期直肠癌：一项随机试验的2期结果（STELLAR II）。

背景：免疫治疗联合新辅助放化疗治疗熟练错配修复(pMMR)/微卫星稳定（MSS）局部晚期直肠癌（LARC）的疗效和模式尚不确定。方法：在这项多中心、随机、无缝的2/3期试验（ClinicalTrials.gov: NCT05484024）中，符合条件的参与者被随机分配（1:1）接受短期放疗（5 Gy × 5），随后接受4个周期卡培他滨和奥沙利铂或6个周期亚叶酸钙、奥沙利铂和氟尿嘧啶，加（iTNT组）或不加（总新辅助治疗[TNT]组）4个周期辛替单抗。在新辅助治疗后，参与者接受手术或基于临床完全缓解的观察和等待策略。主要终点是2期的完全缓解（CR）率和3期的3年无病生存（DFS）率。结果：218例患者随机分为iTNT组（n = 110）和TNT组（n = 108）。所有患者均完成了SCRT，其中iTNT组88.2%，TNT组93.5%完成了4个周期的新辅助治疗。iTNT组的CR率明显更高（45.5% vs. 25.0%; p = 0.003）。iTNT组和TNT组分别有34.5%和19.4%报告了3-4级治疗相关不良事件（p = 0.012），其中血小板减少、腹泻、白细胞减少和中性粒细胞减少是最常见的。iTNT组中5.5%的患者发生了3-4级免疫相关不良事件。结论：与基于sct的TNT相比，PD-1抑制剂sintilimab的加入显著提高了CR率，并且在pMMR/MSS LARC患者中具有良好的耐受性。基金资助：国家自然科学基金（82473248）和深圳市医学研究基金（C2301001）资助。

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来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

期刊介绍： Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.