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

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, Morris Van, Scott Kopetz, Michael Overman and Kaysia Ludford
Additional contact information
Michael LaPelusa: MD Anderson Cancer Center
Wei Qiao: MD Anderson Cancer Center
Bryan Iorgulescu: MD Anderson Cancer Center
Francis San Lucas: MD Anderson Cancer Center
Keyur Patel: MD Anderson Cancer Center
Deepak Bhamidipati: MD Anderson Cancer Center
Jane Varkey Thomas: MD Anderson Cancer Center
Nancy You: MD Anderson Cancer Center
Wai Chin Foo: MD Anderson Cancer Center
Dipen Maru: MD Anderson Cancer Center
Selvi Thirumurthi: MD Anderson Cancer Center
Morris Van: MD Anderson Cancer Center
Scott Kopetz: MD Anderson Cancer Center
Michael Overman: MD Anderson Cancer Center
Kaysia Ludford: MD Anderson Cancer Center

Nature Communications, 2025, vol. 16, issue 1, 1-6

Abstract: 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

Date: 2025
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DOI: 10.1038/s41467-025-59615-3

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