Robust response to pembrolizumab in Temozolomide-Associated Hypermutated and Microsatellite Instability-High Functional Pancreatic Neuroendocrine Tumor

Udhayvir S Grewal; Charles W Shi; Saima Muzahir; Po H Ear; Seth J Concors; Daniel M Halperin

doi:10.1093/oncolo/oyag229

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Robust response to pembrolizumab in Temozolomide-Associated Hypermutated and Microsatellite Instability-High Functional Pancreatic Neuroendocrine Tumor

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Robust response to pembrolizumab in Temozolomide-Associated Hypermutated and Microsatellite Instability-High Functional Pancreatic Neuroendocrine Tumor

Udhayvir S Grewal, Charles W Shi, Saima Muzahir, Po H Ear, Seth J Concors and Daniel M Halperin

The oncologist (Dayton, Ohio), Vol.31(7), oyag229

07/2026

DOI: 10.1093/oncolo/oyag229

PMCID: PMC13302787

PMID: 42296390

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Abstract

Pancreatic neuroendocrine tumors (PanNETs) are typically characterized by low tumor mutational burden (TMB) and limited responsiveness to immune checkpoint inhibitors (ICIs). Emerging evidence suggests that prior exposure to alkylating chemotherapeutic agents may be associated a hypermutated phenotype (along with DNA mismatch repair dysfunction or DNA damage response gene alterations), potentially sensitizing tumors to immunotherapy. We present a case of a 68-year-old woman with metastatic functional PanNET (VIPoma) who developed a treatment-associated hypermutated, microsatellite instability-high (MSIhigh) phenotype following capecitabine-temozolomide (CAPTEM) therapy. Treatment with pembrolizumab resulted in a robust clinical, biochemical, and radiographic response. This case highlights dynamic genomic evolution in PanNETs and underscores the importance of serial molecular profiling in guiding therapeutic decisions.

Details

Title: Subtitle: Robust response to pembrolizumab in Temozolomide-Associated Hypermutated and Microsatellite Instability-High Functional Pancreatic Neuroendocrine Tumor
Creators: Udhayvir S Grewal - University of Iowa Hospitals and Clinics
Charles W Shi - Emory University
Saima Muzahir - Emory University
Po H Ear - University of Iowa, Surgery
Seth J Concors - Emory University
Daniel M Halperin - The University of Texas MD Anderson Cancer Center
Resource Type: Journal article
Publication Details: The oncologist (Dayton, Ohio), Vol.31(7), oyag229
DOI: 10.1093/oncolo/oyag229
PMID: 42296390
PMCID: PMC13302787
NLM abbreviation: Oncologist
ISSN: 1549-490X
eISSN: 1549-490X
Publisher: Oxford University Press
Language: English
Electronic publication date: 06/15/2026
Date published: 07/2026
Academic Unit: Surgery
Record Identifier: 9985173905402771

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