PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer

被引：996

作者：

Cercek, Andrea ^{[1
,2
]}

Lumish, Melissa ^{[2
]}

Sinopoli, Jenna ^{[2
,4
]}

Weiss, Jill ^{[2
]}

Shia, Jinru ^{[2
,3
]}

Lamendola-Essel, Michelle ^{[2
]}

El Dika, Imane H. ^{[2
]}

Segal, Neil ^{[2
]}

Shcherba, Marina ^{[2
]}

Sugarman, Ryan ^{[2
]}

Stadler, Zsofia ^{[2
]}

Yaeger, Rona ^{[2
]}

Smith, J. Joshua

Rousseau, Benoit ^{[2
]}

Argiles, Guillem ^{[2
]}

Patel, Miteshkumar ^{[2
]}

Desai, Avni ^{[2
]}

Saltz, Leonard B. ^{[2
]}

Widmar, Maria ^{[4
]}

Iyer, Krishna ^{[8
]}

Zhang, Janie ^{[8
]}

Gianino, Nicole ^{[8
]}

Crane, Christopher ^{[5
]}

Romesser, Paul B. ^{[5
]}

Pappou, Emmanouil P. ^{[4
]}

Paty, Philip ^{[4
]}

Garcia-Aguilar, Julio ^{[4
]}

Gonen, Mithat ^{[6
]}

Gollub, Marc ^{[7
]}

Weiser, Martin R. ^{[4
]}

Schalper, Kurt A. ^{[8
]}

Diaz, Luis A. ^{[1
,2
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA

[2] Mem Sloan Kettering Canc Ctr, Div Solid Tumor Oncol, New York, NY USA

[3] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY USA

[4] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY USA

[5] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY USA

[6] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY USA

[7] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY USA

[8] Yale Univ Sch Med, Dept Pathol, New Haven, CT USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2022年 / 386卷 / 25期

基金：

美国国家卫生研究院;

关键词：

TOTAL MESORECTAL EXCISION; CHEMORADIATION; MELANOMA; THERAPY; SURGERY; NEOANTIGENS; DYSFUNCTION; SURVIVAL; TUMORS;

D O I：

10.1056/NEJMoa2201445

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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, F-18-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.

引用

页码：2363 / 2376

页数：14

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