Med (New York, N.Y.) · 2025
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).
СтатьяРандомизированное исследованиеКлиническое исследование II фазыМногоцентровое исследованиеКлиническое исследование III фазыПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Tang Yuan, Li Hao-Yue, Wei Li-Chun, Li Ning, Zhang Wen-Jue, Lu Yu-Fei, Deng Fei-Yan, Xu Tong-Zhen, Shuai Jia-Cheng, Lei Zi-Fa, Meng Xian-Yu, Qi Shu-Nan, Song Yong-Wen, Zhang Wen-Wen, Jing Hao, Li Gong, Liu Shi-Xin, Wang Ying-Jie, Liu Zheng, Ma Hui-Ying, Wang Ning-Yu, Chen Bo, Wang Shu-Lian, Li Ye-Xiong, Zhao Li-Na, Tang Jian-Qiang, Jiang Zheng, Chen Ying-Gang, Zhou Hai-Tao, Hu Chen, Jin Jing
Аннотация
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).
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).