Larotrectinib

Indication. Larotrectinib is indicated for adult and pediatric patients with solid tumors and an NTRK gene fusion without a known acquired resistance variant; with disease that is metastatic or where surgical resection is likely to result in severe morbidity; and who have disease progression after treatment and have no satisfactory alternative treatment options.

Evidence. U.S. Food and Drug Administration (FDA) approval was based on data from three multicenter, open-label, single-arm clinical trials: LOXO-TRK-14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431).[3,4][Level of evidence C3]

Efficacy. Among 55 patients with unresectable or metastatic solid tumors harboring an NTRK gene fusion enrolled across the three trials, the overall response rate was 75% (95% CI, 61%–85%). The complete response rate was 22%, and the partial response rate was 53%. The median follow-up was 8.3 months.[3,5]

Identification of biomarker. NTRK gene fusion status was prospectively determined at local laboratories using next-generation sequencing (NGS) or fluorescence in situ hybridization (FISH). Not all NTRK variants are gene fusions. Entrectinib has not shown clinical efficacy in patients with nonfusion NTRK variants..