Faculty, Staff and Student Publications
Publication Date
5-15-2025
Journal
Nature Communications
Abstract
Neoadjuvant immunotherapy can induce pathologic complete response (pCR) in patients with localized deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) tumors. The long-term outcomes of these patients are unknown, as is the clinical utility of measuring circulating tumor DNA (ctDNA). Follow-up was evaluated in patients enrolled in a phase II trial (NCT04082572) that evaluated the efficacy and safety of pembrolizumab in patients with localized dMMR/MSI-H tumors. The primary outcomes of this trial have previously been reported. 3-year EFS and OS rates were 80% (95% CI: 66% - 93%) and 94% (95% CI: 86% - 100%). Patients without detectable ctDNA after pembrolizumab had higher 3-year EFS and OS rates than patients with detectable ctDNA after pembrolizumab (3-year EFS 92% vs 20%; p < 0.001, 3-year OS 100% vs 80%; p < 0.001). Patients with colorectal cancer (CRC) who had undetectable ctDNA after pembrolizumab were more likely to have pCR compared to those with detectable ctDNA after pembrolizumab (91% vs 0%; p = 0.03). Patients with CRC who were managed non-operatively and had undetectable ctDNA after pembrolizumab had a higher 2-year EFS rate than patients with detectable ctDNA after pembrolizumab (100% vs 33%; p = 0.03). Pembrolizumab demonstrates long-term efficacy in patients with localized dMMR/MSI-H tumors.
Keywords
Humans, Antibodies, Monoclonal, Humanized, Circulating Tumor DNA, Female, Male, Middle Aged, DNA Mismatch Repair, Microsatellite Instability, Aged, Adult, Antineoplastic Agents, Immunological, Treatment Outcome, Neoplasms, Colorectal Neoplasms, Neoadjuvant Therapy
DOI
10.1038/s41467-025-59615-3
PMID
40374594
PMCID
PMC12081696
PubMedCentral® Posted Date
5-15-2025
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons