Long-Term Efficacy of Pembrolizumab and the Clinical Utility of ctDNA in Locally Advanced dMMR/MSI-H Solid Tumors

Long-Term Efficacy of Pembrolizumab and the Clinical Utility of ctDNA in Locally Advanced dMMR/MSI-H Solid Tumors

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Michael LaPelusa, Wei Qiao, Bryan Iorgulescu, Francis San Lucas, Keyur Patel, Deepak Bhamidipati, Jane Varkey Thomas, Nancy You, Wai Chin Foo, Dipen Maru, Selvi Thirumurthi, Van Morris, Scott Kopetz, Michael Overman, Kaysia Ludford
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-59615-3
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2041-1723

Similar Items