Curative immune checkpoint inhibitors therapy in patients with mismatch repair-deficient locally advanced rectal cancer: a real-world observational study

IF 7.1 2区医学 Q1 ONCOLOGY

ESMO Open Pub Date : 2024-10-01 DOI:10.1016/j.esmoop.2024.103929

F. Tosi , L. Salvatore , E. Tamburini , S. Artale , S. Lonardi , S. Marchetti , A. Pastorino , F. Pietrantonio , A. Puccini , F.L. Rojas-Llimpe , B. Vincenzi , S. Mariano , F. Negri , K. Bencardino , C. Pinto , C. Aschele , S. Siena

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引用次数: 0

Abstract

Background

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.

Materials and methods

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).

Results

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.

Conclusion

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.

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错配修复缺陷局部晚期直肠癌患者的治愈性免疫检查点抑制剂治疗：一项真实世界观察研究。

背景：据报道，在最近的一项II期研究中，23例错配修复缺陷/微卫星不稳定（dMMR/MSI）局部晚期直肠癌（LARC）患者均在单用多司他利单抗治疗后获得了持续的临床完全缓解。这些结果导致多司他利单抗或其他免疫检查点抑制剂（ICIs）甚至在监管机构批准之前就被用于dMMR/MSI-LARC的标签外治疗。本研究[STAR(t)-IT-REDUCE]描述了意大利接受 ICI 治疗的 dMMR/MSI-LARC 患者的疗效：由研究者发起的对dMMR/MSI-LARC患者进行ICI治疗的多中心观察性、回顾性队列研究。如果患者在2022年7月至2023年12月（意大利批准多司他利单抗用于该适应症的日期）期间接受过≥1次ICI治疗，则符合研究条件：17名dMMR/MSI-LARC患者（17名治疗无效患者中的13名）符合条件。14名患者完成了6个月的治疗，2名患者在服药4次后停药，1名患者在服药5次后停药，停药原因分别是免疫相关肺炎、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 人[94.1%；95% 置信区间 (CI) 69.24% 至 99.69%，"ITT 分析"]获得了完全临床应答 (cCR)。在完成6个月治疗的11名治疗无效患者中，有10人获得了cCR（90.9%；95% CI为57.12%至99.52%，"按方案分析"）。一名接近 CCR 的患者接受了直肠手术，发现了极少残留的黏膜内肿瘤。中位随访 9.5 个月，未出现局部复发。一名患者出现了未经证实的肺转移。两例3级不良反应，无4级不良反应：本 STAR(t)-IT-REDUCE 研究证实了 ICI 单药治疗 dMMR/MSI-LARC 的免疫消融和治疗活性。现实世界中固有的毒性和依从性问题是有限的，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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.