Initial US Approval
20181,2
Indications
The treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or have progressed following treatment. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1
Recommended Dose/Route
Adult and pediatric patients with a body surface area ≥1.0 m2, 100 mg orally twice daily. Adult and pediatric patients with a body surface area <1.0 m2, 100 mg/m2 orally twice daily.1
Larotrectinib: Dose Reductions for Adverse Reactions
Pivotal Studies1,3
LOXO-TRK-14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431)
Key Inclusion Criteria: Eligible patients had a locally advanced or metastatic solid tumor, had received standard therapy previously, had an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-3, and had adequate major organ function.3
Treatment
Larotrectinib 100 mg/m2 orally twice daily (BSA <1.0 m2), or Larotrectinib 100 mg orally twice daily (BSA ≥1.0 m2) until disease progression, unacceptable level of adverse events, or withdrawal from the study.1
Larotrectinib: Efficacy Data
Safety
The most common adverse reactions (≥ 20%) include fatigue, nausea, dizziness, vomiting, anemia, increased ALT, constipation, and diarrhea.The most common laboratory abnormalities (≥5%) include increased ALT, increased AST, hypoalbuminemia, increase alkaline phosphatase, anemia, neutropenia.1
Dosage Interruption Due to Adverse Events (AEs): 37%1
Permanent Discontinuation Due to AEs: 13%1
References
1. Vitraki (Larotrectinib) [Package Insert]. Loxo Oncology; 2018.
2. FDA approves larotrectinib for solid tumors with NTRK gene fusions | FDA. Accessed March 18, 2024. https://www.fda.gov/drugs/fda-approves-larotrectinib-solid-tumors-ntrk-gene-fusions
3. Drilon A, Laetsch TW, Kummar S, et al. Efficacy of Larotrectinib in TRK Fusion–Positive Cancers in Adults and Children. N Engl J Med. 2018;378(8):731-739. doi:10.1056/NEJMoa1714448