Nonoperative Management of Mismatch Repair–Deficient Tumors

作者：Andrea Cercek, Michael Bonner Foote, Benoı̂t Rousseau, Jesse Joshua Smith, Jinru Shia, Jenna Sinopoli, Jill A. Weiss, Melissa Amy Lumish, Lindsay Temple, Mitesh Patel, Callahan M. Wilde, Leonard B. Saltz, Guillem Argilés, Zsofia Kinga Stadler, Oliver Artz, Steven Brad Maron, Geoffrey Yuyat Ku, Ping Gu, Yelena Yuriy Janjigian, Daniela Molena, Gopa Iyer, Jonathan Coleman, Wassim M. Abida, Seth Cohen, Kevin C. Soares, Mark Andrew Schattner, Vivian E. Mack Strong, Rona D. Yaeger, Philip B. Paty, Marina Shcherba, Ryan Sugarman, Paul Bernard Romesser, Alice Zervoudakis, Avni Mukund Desai, Neil Howard Segal, Imane El Dika, Maria Widmar, Iris H. Wei, Emmanouil Pappou, Gerard Fumo, Santiago Aparo, Mithat Gönen, Marc Jeffrey Gollub, Vetri S. Jayaprakasham, Tae-Hyung Kim, Julio García Aguilar, Martin Weiser, Luis Alberto Diaz · 发表于：New England Journal of Medicine · 年份：2025 · DOI：10.1056/nejmoa2404512 · 被引用次数：216 · 研究领域：Genetic factors in colorectal cancer、Multiple and Secondary Primary Cancers、Colorectal Cancer Surgical Treatments

BACKGROUND: Among patients with mismatch repair-deficient (dMMR), locally advanced rectal cancer, neoadjuvant checkpoint blockade eliminated the need for surgery in a high proportion of patients. Whether this approach can be extended to all early-stage dMMR solid tumors, regardless of tumor site, is unknown. METHODS: We conducted a phase 2 study in which patients with stage I, II, or III dMMR solid tumors that were amenable to curative-intent surgery were treated with neoadjuvant dostarlimab, a programmed cell death 1 (PD-1) blocking agent, for 6 months. The response to treatment was assessed in two cohorts: patients in cohort 1 had dMMR, locally advanced rectal cancer, and patients in cohort 2 had dMMR nonrectal solid tumors. Patients with a clinical complete response could elect to proceed with nonoperative management; those with residual disease were to undergo resection. In this analysis, the primary end point, assessed in cohort 1, was a sustained clinical complete response at 12 months. Recurrence-free survival and safety were evaluated. RESULTS: A total of 117 patients were included in the analysis. In cohort 1, all 49 patients who completed treatment had a clinical complete response and elected to proceed with nonoperative management. A total of 37 patients had a sustained clinical complete response at 12 months, a finding that met the criterion for efficacy. In cohort 2, a total of 35 of 54 patients who completed treatment had a clinical complete response, and 33 ele...