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Larotrectinib in Mismatch-Repair-Deficient TRK Fusion-Positive Metastatic Colon Cancer After Progression on Immunotherapy
Journal article   Open access   Peer reviewed

Larotrectinib in Mismatch-Repair-Deficient TRK Fusion-Positive Metastatic Colon Cancer After Progression on Immunotherapy

Pashtoon M Kasi, Maaz Khan Afghan, Andrew M Bellizzi and Carlos H F Chan
Cureus, Vol.14(7), e26648
07/07/2022
DOI: 10.7759/cureus.26648
PMCID: PMC9270193
PMID: 35815302
url
https://doi.org/10.7759/cureus.26648View
Published (Version of record) Open Access

Abstract

Case report. A 43-year-old woman presented with recurrent metastatic colon cancer with metastases to the peritoneum after having initially been diagnosed with stage IIB colon cancer and deferring adjuvant chemotherapy. Circulating tumor DNA (ctDNA)-based liquid biopsy testing revealed microsatellite instability-high (MSI-H) status, which was also confirmed on tissue testing. This patient then underwent four cycles of pembrolizumab and two cycles of ipilimumab and nivolumab (CTLA-4 rescue) with, unfortunately, progression of the disease. The patient was subsequently treated with larotrectinib, given the findings of TRK fusion-positive cancer on next-generation sequencing (NGS), and she was able to undergo curative surgery two months later that showed complete pathologic response. She continues to have no evidence of disease years later as well as no detectable ctDNA on NGS as well as tumor-informed minimal residual disease platforms. This case represents a marked and durable response to larotrectinib in a patient with deficiency in mismatch repair/MSI-H metastatic colorectal cancer harboring an NTRK fusion, bringing to light the potential for use of larotrectinib in earlier treatment lines in patients, and/or choice of targeted therapy versus immunotherapy in this patient subset.

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