AI Article Synopsis

  • The study investigates pancreatic cancer (PC) with deficient mismatch repair (dMMR) and high microsatellite instability (MSI-H), which show poor outcomes and few treatment options, particularly focusing on responses to immune checkpoint inhibitors (ICIs).
  • Researchers reviewed records of 32 patients diagnosed with dMMR/MSI-H PC, observing favorable outcomes with ICIs, including a 75% overall response rate in palliative care, compared to only 30% with conventional chemotherapy.
  • The findings suggest that ICIs should be prioritized over cytotoxic chemotherapy for patients with dMMR/MSI-H PC in need of systemic therapy, highlighting discrepancies in testing methods used for MMR and MSI.

Article Abstract

Purpose: Pancreatic cancer (PC) carries a poor prognosis with high rates of unresectable/metastatic disease at diagnosis, recurrence after resection, and few systemic therapy options. Deficient mismatch repair (dMMR)/high microsatellite instability (MSI-H) PCs demonstrated uncharacteristically poor outcomes in KEYNOTE-158, evaluating pembrolizumab in MSI-H solid tumors. Our study aggregates the Mayo Clinic experience with dMMR/MSI-H PCs, characterizing the clinical, molecular, and treatment response patterns with a focus on response to immune checkpoint inhibitors (ICIs).

Methods: Retrospective data were collected from the electronic medical record from December 2009 to February 2023. Patients were included if they had a pathologically confirmed pancreatic malignancy and had (1) deficient expression of mismatch repair (MMR) proteins by tumor immunohistochemistry, (2) pathogenic mutation of MMR genes on genomic sequencing, and/or (3) MSI-H by polymerase chain reaction.

Results: Thirty-two patients were identified for inclusion, with all stages of disease represented. Sixteen of these patients underwent surgery or chemoradiotherapy. Of these patients, uncharacteristically favorable responses were seen, with a recurrence rate of only 19% (n = 3) despite a median follow-up of 25 months. In the palliative setting, excellent responses to ICI were seen, with overall response rate (ORR) of 75% (20% complete response). Median time to disease progression was not reached. Response rates to cytotoxic chemotherapy in the palliative setting were poor, with 30% ORR and median time to progression of 4 months. We observed a high rate of discrepancy between MMR and MSI testing methods, representing 19% of the entire cohort and 26% of evaluable cases.

Conclusion: Our data argue for the preferential use of ICI over cytotoxic chemotherapy in any patient with dMMR/MSI-H PC requiring systemic therapy, including in the metastatic and adjuvant/neoadjuvant settings.

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Source
http://dx.doi.org/10.1200/PO.22.00706DOI Listing

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