Synapse - Nonoperative management of mismatch repair-deficient tumors

Nonoperative management of mismatch repair-deficient tumors Journal Article

Authors:	Cercek, A.; Foote, M. B.; Rousseau, B.; Smith, J. J.; Shia, J.; Sinopoli, J.; Weiss, J.; Lumish, M.; Temple, L.; Patel, M.; Wilde, C.; Saltz, L. B.; Argiles, G.; Stadler, Z.; Artz, O.; Maron, S.; Ku, G.; Gu, P.; Janjigian, Y. Y.; Molena, D.; Iyer, G.; Coleman, J.; Abida, W.; Cohen, S.; Soares, K.; Schattner, M.; Strong, V. E.; Yaeger, R.; Paty, P.; Shcherba, M.; Sugarman, R.; Romesser, P. B.; Zervoudakis, A.; Desai, A.; Segal, N. H.; El Dika, I.; Widmar, M.; Wei, I.; Pappou, E.; Fumo, G.; Aparo, S.; Gonen, M.; Gollub, M.; Jayaprakasam, V. S.; Kim, T. H.; Garcia Aguilar, J.; Weiser, M.; Diaz, L. A. Jr
Article Title:	Nonoperative management of mismatch repair-deficient tumors
Abstract:	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 elected to proceed with nonoperative management. Among the 103 patients who completed treatment across both cohorts, 84 had a clinical complete response, and 82 did not undergo surgery. Among the 117 total patients, recurrence-free survival at 2 years was 92% (95% confidence interval, 86 to 99); the median follow-up for recurrence was 20.0 months (range, 0 to 60.8). The majority of patients (95%) had reversible, grade 1 or 2 adverse events (60%) or had no adverse events (35%). The option for curative resection was not compromised during or after treatment in any of the patients. Conclusions Among patients with early-stage dMMR solid tumors that were amenable to curative-intent surgery, neoadjuvant PD-1 blockade led to organ preservation in a high proportion of patients. (Funded by Swim Across America and others; ClinicalTrials.gov number, NCT04165772). © 2025 Massachusetts Medical Society.
Keywords:	surgery; gastroenterology; hematology/oncology; gastrointestinal tract cancer; treatments in oncology; surgery general
Journal Title:	New England Journal of Medicine
Volume:	392
Issue:	23
ISSN:	0028-4793
Publisher:	Massachusetts Medical Society
Date Published:	2025-06-19
Start Page:	2297
End Page:	2308
Language:	English
DOI:	10.1056/NEJMoa2404512
PUBMED:	40293177
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-105008676130&doi=10.1056%2fNEJMoa2404512&partnerID=40&md5=30f01be16384fb10b5403e9aa6fed987
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding authors are Andrea Cercek and Luis Diaz Jr -- Source: Scopus