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Case Report|Articles in Press, 100501

Primary Resistance to Larotrectinib in a Patient with Squamous Non-Small Cell Lung Cancer with Subclonal NTRK1 Fusion: Case Report

Open AccessPublished:March 17, 2023DOI:https://doi.org/10.1016/j.jtocrr.2023.100501
Primary Resistance to Larotrectinib in a Patient with Squamous Non-Small Cell Lung Cancer with Subclonal NTRK1 Fusion: Case Report
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      Abstract

      The neurotrophic receptor tyrosine kinase (NTRK) genes encode the tropomyosin receptor kinase (TRK) proteins. NTRK fusions lead to constitutively active, ligand-independent downstream signaling. NTRK fusions are implicated in up to 1% of all solid tumors and 0.2% of non-small cell lung cancer (NSCLC). Larotrectinib, a highly selective small molecule inhibitor of all three TRK proteins, has a response rate of 75% across a wide range of solid tumors. Mechanisms of primary resistance to larotrectinib are not well understood. We report a case of a 75-year-old male with minimal smoking history with NTRK fusion-positive metastatic squamous NSCLC with primary resistance to larotrectinib. We suggest subclonal NTRK fusion as a possible mechanism contributing to primary resistance to larotrectinib.

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      Publication history

      Accepted: March 12, 2023
      Received in revised form: February 13, 2023
      Received: November 13, 2022

      Publication stage

      In Press Journal Pre-Proof

      Footnotes

      Disclosure Statement of Conflict of Interest:

      MCB has no disclosures. JST has research funding from Blue Note Therapeutics to MGH. MMK has served as a compensated consultant for AstraZeneca, Sanofi, BMS, and Janssen Oncology and received loyalties from Elsevier, not related to the current case. LLR has received honoraria from PeerView, Medscape, Clinical Care Options, consulting honoraria from Abbvie, Personal Genome Diagnostics, Bristol Myers Squibb, Loxo Oncology at Lilly, Amgen, Merck, AstraZeneca, Sanofi-Genzyme, and EMD Serono. IDJ has received honoraria from Foundation Medicine, Creative Education Concepts, OncLive, ASCO Post, DAVA Oncology, Medscape, Total Health, Triptych Health Partners, and Aptitude Health, American Lung Association, consulting fees from AstraZeneca, Boehringer Ingelheim, Bayer, BostonGene, Bristol Myers Squibb, Catalyst, Genentech, Janssen, Novocure, Pfizer, Sanofi-Genzyme, Syros, and Xcovery, research support from Array, Genentech, Novartis, Pfizer, and Guardant Health, and travel support from Array and Pfizer.

      MCB: Writing - original draft and review and editing. JST: Writing - review and editing. MMK: Writing - review and editing, resources. LLR: Writing - review and editing, resources. IDJ: Conceptualization, writing - original draft and review and editing.

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      DOI: https://doi.org/10.1016/j.jtocrr.2023.100501

      Copyright

      © 2023 Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer.

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