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Mechanisms of acquired resistance

These three clinical trials (LOXO-TRK-14001, SCOUT and NAVIGATE) also investigated the mechanisms of acquired resistance to larotrectinib (i.e. disease progression during treatment after a documented objective response or stable disease for ≥6 months), which was observed in 10 patients and further characterised in 9 patients [1]. These included solvent-front substitutions in 7 patients, gatekeeper substitutions in 2 patients, and xDFG substitutions in 2 patients. Three patients had more than one acquired resistance mutation. Among these 10 patients, 80% continued treatment with larotrectinib beyond progression because of ongoing clinical benefit.


  1. Loxo Oncology. VITRAKVI® (larotrectinib) [prescribing information]. In. Stamford, CT: Loxo Oncology, Inc. 2018.

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