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PD-1阻断治疗错配修复缺陷型局部晚期直肠癌安全有效
作者:小柯机器人 发布时间:2022/6/7 16:49:48

美国纪念斯隆·凯特林癌症中心Andrea Cercek团队研究了PD-1阻断治疗错配修复缺陷型局部晚期直肠癌的疗效。2022年6月5日出版的《新英格兰医学杂志》发表了这项成果。

直肠手术切除后的新辅助化疗和放疗是局部晚期直肠癌的标准治疗方法。直肠癌的一个亚组是由错配修复缺陷引起的。由于错配修复缺陷型结直肠癌在转移性疾病的情况下对程序性死亡1(PD-1)阻断有反应,因此研究组假设检查点阻断对错配修复缺陷型局部晚期直肠癌患者有效。

研究组启动了一项前瞻性临床2期研究,在该研究中,错配修复缺陷型II或III期直肠腺癌患者每3周服用一次抗PD-1单克隆抗体多塔利单抗,为期6个月。该治疗之后是标准化放疗和手术。完成多塔利单抗治疗后临床完全缓解的患者将不进行放化疗和手术。主要终点为完成多塔利单抗治疗12个月后的持续临床完全缓解,或完成多塔利单抗治疗加或不加放化疗后的病理完全缓解,以及对新辅助多塔利单抗治疗加或不加放化疗的总体缓解。

共有12名患者完成了多塔利单抗治疗,并进行了至少6个月的随访。所有12名患者(100%)临床完全缓解,磁共振成像、18F-氟脱氧葡萄糖-正电子发射断层扫描、内窥镜评估、直肠指检或活检均无肿瘤证据。在该研究发表时,没有患者接受过放化疗或手术,随访期间(6至25个月)也没有报告恶化或复发的病例。未报告3级或以上不良事件。

研究结果表明,错配修复缺陷型局部晚期直肠癌对单药PD-1阻断高度敏感。需要更长的随访时间来评估缓解的持续时间。

附:英文原文

Title: PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer | NEJM

Author: Andrea Cercek, M.D.,, Melissa Lumish, M.D.,, Jenna Sinopoli, N.P.,, Jill Weiss, B.A.,, Jinru Shia, M.D.,, Michelle Lamendola-Essel, D.H.Sc.,, Imane H. El Dika, M.D.,, Neil Segal, M.D.,, Marina Shcherba, M.D.,, Ryan Sugarman, M.D., Ph.D.,, Zsofia Stadler, M.D.,, Rona Yaeger, M.D.,, J. Joshua Smith, M.D., Ph.D.,, Benoit Rousseau, M.D., Ph.D.,, Guillem Argiles, M.D.,, Miteshkumar Patel, M.S.,, Avni Desai, M.D.,, Leonard B. Saltz, M.D.,, Maria Widmar, M.D.,, Krishna Iyer, M.D., Ph.D.,, Janie Zhang, M.D.,, Nicole Gianino, M.S.,, Christopher Crane, M.D.,, Paul B. Romesser, M.D.,, Emmanouil P. Pappou, M.D., Ph.D.,, Philip Paty, M.D.,, Julio Garcia-Aguilar, M.D.,, Mithat Gonen, Ph.D.,, Marc Gollub, M.D.,, Martin R. Weiser, M.D.,, Kurt A. Schalper, M.D., Ph.D.,, and Luis A. Diaz, Jr., M.D.

Issue&Volume: 2022-06-05

Abstract:

Background

Neoadjuvant chemotherapy and radiation followed by surgical resection of the rectum is a standard treatment for locally advanced rectal cancer. A subset of rectal cancer is caused by a deficiency in mismatch repair. Because mismatch repair–deficient colorectal cancer is responsive to programmed death 1 (PD-1) blockade in the context of metastatic disease, it was hypothesized that checkpoint blockade could be effective in patients with mismatch repair–deficient, locally advanced rectal cancer.

Methods

We initiated a prospective phase 2 study in which single-agent dostarlimab, an anti–PD-1 monoclonal antibody, was administered every 3 weeks for 6 months in patients with mismatch repair–deficient stage II or III rectal adenocarcinoma. This treatment was to be followed by standard chemoradiotherapy and surgery. Patients who had a clinical complete response after completion of dostarlimab therapy would proceed without chemoradiotherapy and surgery. The primary end points are sustained clinical complete response 12 months after completion of dostarlimab therapy or pathological complete response after completion of dostarlimab therapy with or without chemoradiotherapy and overall response to neoadjuvant dostarlimab therapy with or without chemoradiotherapy.

Results

A total of 12 patients have completed treatment with dostarlimab and have undergone at least 6 months of follow-up. All 12 patients (100%; 95% confidence interval, 74 to 100) had a clinical complete response, with no evidence of tumor on magnetic resonance imaging, 18F-fluorodeoxyglucose–positron-emission tomography, endoscopic evaluation, digital rectal examination, or biopsy. At the time of this report, no patients had received chemoradiotherapy or undergone surgery, and no cases of progression or recurrence had been reported during follow-up (range, 6 to 25 months). No adverse events of grade 3 or higher have been reported.

Conclusions

Mismatch repair–deficient, locally advanced rectal cancer was highly sensitive to single-agent PD-1 blockade. Longer follow-up is needed to assess the duration of response.

DOI: 10.1056/NEJMoa2201445

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2201445

 

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home