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    Association details:
    Biomarker:MSI-H/dMMR + NTRK2 fusion
    Cancer:Colorectal Cancer
    Drug:Vitrakvi (larotrectinib) (TrkB receptor inhibitor, TrkC kinase inhibitor, TrkA receptor inhibitor)
    Direction:Sensitive
    Evidence:
    Evidence Level:
    Sensitive: C3 – Early Trials
    Source:
    ESMO-GI 2023
    Title:

    Long-term efficacy and safety of larotrectinib in patients with tropomyosin receptor kinase (TRK) fusion gastrointestinal (GI) cancer: An updated analysis

    Published date:
    06/27/2023
    Excerpt:
    Patients with TRK fusion GI cancer enrolled in the phase II larotrectinib clinical trial NAVIGATE (NCT02576431) were included….Among the patients with CRC, 14 were microsatellite instability-high (MSI-H)….Of the nine responders, five were MSI-H. Median DoR, PFS and OS for all IRC-eligible patients with CRC was 27.3 months (95% CI 5.6e NE), 29.4 months (95%CI5.4e NE) and 29.4 months (95% CI6.1e NE)....With longer follow-up , larotrectinib continued to demonstrate long lasting responses, extended survival and a favourable safety profile in patients with TRK fusion GI cancer, particularly in those with MSI-H CRC.
    DOI:
    https://doi.org/10.1016/j.annonc.2023.04.055
    Trial ID:
    NAVIGATE
    Evidence Level:
    Sensitive: C3 – Early Trials
    Source:
    ESMO-GI 2021
    Title:

    SO-29 Efficacy and safety of larotrectinib in patients with tropomyosin receptor kinase fusion-positive gastrointestinal cancer: An expanded dataset

    Published date:
    07/04/2021
    Excerpt:
    As of July 20, 2020, 18 patients with metastatic TRK fusion-positive GI cancer were enrolled...Of the 10 patients with CRC, 7 were microsatellite instability-high (MSI-H)...In the 10 patients with CRC, ORR was 50% (95% CI 19–81): 1 CR, 4 PR (1 pending confirmation), and 5 SD.
    DOI:
    10.1016/j.annonc.2021.05.053
    Trial ID:
    NAVIGATE
    Evidence Level:
    Sensitive: C4 – Case Studies
    Source:
    Cureus
    Title:

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

    Published date:
    07/07/2022
    Excerpt:
    A 43-year-old woman presented with recurrent metastatic colon cancer...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.
    DOI:
    10.7759/cureus.26648