在最近的一项 II 期研究中，所有 23 名错配修复缺陷/微卫星不稳定 (dMMR/MSI) 局部晚期直肠癌 (LARC) 患者仅接受 dostarlimab 治疗，均获得持续的临床完全缓解。这些结果导致甚至在监管部门批准之前就在 dMMR/MSI-LARC 中超说明书使用 dostarlimab 或其他免疫检查点抑制剂 (ICIs)。本研究 [STAR(t)-IT-REDUCE] 描述了在意大利接受 ICI 治疗的 dMMR/MSI-LARC 患者的结果。研究者发起的 dMMR/MSI-LARC ICI 治疗的观察性、回顾性队列、多中心研究。如果在 2022 年 7 月至 2023 年 12 月（意大利批准 dostarlimab 用于该适应症的日期）期间接受≥1 ICI 剂量的患者，则符合资格。17 名 dMMR/MSI-LARC 患者（17 名未接受治疗的患者中的 13 名）符合资格。 14 名患者完成了 6 个月的治疗，其中两名患者在四次给药后停药，一名患者在五次给药后停药，分别因为免疫相关肺炎、社会限制或非肿瘤性肠梗阻。总体而言，17 名可评估患者中有 16 名 [94.1%； 95% 置信区间 (CI) 69.24% 至 99.69%，“ITT 分析”] 实现了完全临床缓解 (cCR)。完成 6 个月治疗的 11 名初治患者中有 10 名达到 cCR（90.9%；95% CI 57.12% 至 99.52%，“符合方案分析”）。 1 例近 CR 患者接受直肠手术，发现粘膜内肿瘤残留极少。中位随访9.5个月，未出现局部复发。一名患者出现未经证实的肺转移。报告了两例 3 级不良事件，没有报告 4 级不良事件。目前的 STAR(t)-IT-REDUCE 研究记录了 ICI 单药疗法在 dMMR/MSI-LARC 中的免疫消融和治疗活性。现实世界实践中固有的毒性和合规性问题是有限的，不会影响初始完全肿瘤反应的实现，但可能会限制反应持续时间。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

Sustained clinical complete remissions were reported in all of 23 mismatch repair deficient/microsatellite instable (dMMR/MSI) locally advanced rectal cancer (LARC) patients treated with dostarlimab alone in a recent phase II study. These results led to off-label use of dostarlimab or other immune checkpoint inhibitors (ICIs) in dMMR/MSI-LARC even before regulatory approval. The present study [STAR(t)-IT-REDUCE] describes the outcome of dMMR/MSI-LARC patients treated with ICI in Italy.Investigator-initiated, observational, retrospective-cohort, multicentric study of ICI treatment in dMMR/MSI-LARC. Patients were eligible if treated with ≥1 ICI dose from July 2022 to December 2023 (date of approval of dostarlimab for this indication in Italy).Seventeen dMMR/MSI-LARC patients (13 of 17 treatment-naïve) were eligible. Fourteen patients completed 6 months of treatment, two discontinued after four doses and one after five doses because of immune-related pneumonia, social constraints, or non-oncological bowel obstruction, respectively. Overall, 16 of 17 assessable patients [94.1%; 95% confidence interval (CI) 69.24% to 99.69%, 'ITT analysis'] achieved complete clinical response (cCR). Ten of 11 treatment-naïve patients completing 6 months of treatment had cCR (90.9%; 95% CI 57.12% to 99.52%, 'per-protocol analysis'). One patient with near-CR underwent rectal surgery and minimal residual intramucosal tumor was found. With a median follow-up of 9.5 months, no local relapse occurred. One patient developed unconfirmed lung metastases. Two grade 3 and no grade 4 adverse events were reported.The present STAR(t)-IT-REDUCE study documents the immunoablative and curative activity of ICI monotherapy in dMMR/MSI-LARC. Toxicity and compliance issues inherent to real-world practice are limited and do not affect achievement of initial complete tumor response but may limit response duration.Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.