Randomized Phase II Trial of Immunotherapy-Based Total Neoadjuvant Therapy for Proficient Mismatch Repair or Microsatellite Stable Locally Advanced Rectal Cancer (TORCH)

作者：Fan Xia, Yaqi Wang, Hui Wang, Lijun Shen, Zuo‐Lin Xiang, Yutian Zhao, Huojun Zhang, Juefeng Wan, Hui Zhang, Yan Wang, Ruiyan Wu, Jingwen Wang, Yang Wang, Menglong Zhou, Shujuan Zhou, Yajie Chen, Zhiyuan Zhang, Xian Wu, Yan Xuan, Renjie Wang, Yiqun Sun, Tong Tong, Xun Zhang, Lei Wang, Dan Huang, Weiqi Sheng, Hao Yan, Yang Xu, Yuxin Shen, Yu Xu, Ruping Zhao, Miao Mo, Guoxiang Cai, Sanjun Cai, Ye Xu, Zhen Zhang · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.23.02261 · 被引用次数：118 · 研究领域：Colorectal Cancer Surgical Treatments、Colorectal and Anal Carcinomas、Genetic factors in colorectal cancer

PURPOSE To assess whether the integration of PD-1 inhibitor with total neoadjuvant therapy (iTNT) can lead to an improvement in complete responses (CRs) and favors a watch-and-wait (WW) strategy in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). PATIENTS AND METHODS We conducted a prospective, multicenter, randomized, open-label, phase II trial using a pick-the-winner design. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma were randomly assigned to group A for short-course radiotherapy (SCRT) followed by six cycles of consolidation immunochemotherapy with capecitabine and oxaliplatin and toripalimab or to group B for two cycles of induction immunochemotherapy followed by SCRT and the rest four doses. Either total mesorectal excision or WW was applied on the basis of tumor response. The primary end point was CR which included pathological CR (pCR) after surgery and clinical CR (cCR) if WW was applicable, with hypothesis of an increased CR of 40% after iTNT compared with historical data of 25% after conventional TNT. RESULTS Of the 130 patients enrolled, 121 pMMR/MSS patients were evaluable (62 in group A and 59 in group B). At a median follow-up of 19 months, CR was achieved at 56.5% in group A and 54.2% in group B. Both groups fulfilled the predefined statistical hypothesis ( P < .001). Both groups reported a pCR rate of 50%. Respectively, 15 patients in each group underwent WW and rem...