Initial US Approval

  • 20181

Indications

NTRK+ Solid Tumors:

  • The treatment of adult and pediatric patients with solid tumors that1:
    • 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 that have progressed following treatment.
    • Select patients for therapy based on an FDA-approved test. 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.

Recommended Dose/Route

  • Adult and pediatric patients with a body surface area ≥1.0 m2, 100 mg orally twice daily, with or without food.1
  • Adult and pediatric patients with a body surface area <1.0 m2, 100 mg/m2 orally twice daily, with or without food.1
Larotrectinib: Dose Reduction

Larotrectinib: Dose Reduction

Pivotal Studies

LOXO-TRK-140012 (NCT02122913), SCOUT3 (NCT02637687), and NAVIGATE4 (NCT02576431)

  • Key Inclusion Criteria: Eligible patients were required to have unresectable or metastatic solid tumors with a NTRK gene fusion. All patients were also required to have progressed following systemic therapy for their disease, if available, or would have required surgery with significant morbidity for locally advanced disease.1
  • Treatment: Adult patients received larotrectinib 100 mg orally twice daily and pediatric patients (18 years or younger) received larotrectinib 100 mg/m2 up to a maximum dose of 100 mg orally twice daily until unacceptable toxicity or disease progression.1
Larotrectinib: Efficacy Data

Larotrectinib: Efficacy Data

Safety

LOXO-TRK-140012, SCOUT3, and NAVIGATE4

  • Common Adverse Reactions (≥20%): the most frequently reported adverse events (AEs) were musculoskeletal pain (42%), fatigue (36%), cough (32%), dizziness (27%), constipation (27%), diarrhea (27%), nausea (25%), vomiting (25%), pyrexia (24%), and abdominal pain (21%).1
  • Common Laboratory Abnormalities (≥20%): the most frequently reported laboratory abnormalities were increased AST (52%), increased ALT (45%), anemia (42%), neutropenia (36%), hypoalbuminemia (36%), increased alkaline phosphatase (34%), leukopenia (28%), hypocalcemia (25%), and lymphopenia (22%).1
  • Dosage Interruption Due to AEs: 39%1
  • Dosage Modification Due to AEs: 8%1
  • Permanent Discontinuation Due to AEs: 9%1
Larotrectinib: Most Common Adverse Events of Grade 3 or 4

Larotrectinib: Most Common Adverse Events of Grade 3 or 4

References

  1. Vitrakvi (larotrectinib). Prescribing information. Bayer Pharmaceuticals Inc.; December 2023. Accessed November 18, 2024. https://labeling.bayerhealthcare.com/html/products/pi/vitrakvi_PI.pdf
  2. Laetsch TW, DuBois SG, Mascarenhas L, et al. Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study. Lancet Oncol. 2018;19(5):705-714. doi:10.1016/S1470-2045(18)30119-0
  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
  4. Martineau C, Turcotte MK, Otis N, et al. Management of adverse events related to first-generation tyrosine receptor kinase inhibitors in adults: a narrative review. Support Care Cancer. 2022;30(12):10471-10482. doi: 10.1007/s00520-022-07401-y
  5. Lim JSJ, Tan DSP. TRK inhibitors: managing on-target toxicities. Ann Oncol. 2020;31(9):1109-1111. doi:10.1016/j.annonc.2020.06.010
  6. Liu D, Flory J, Lin A, et al. Characterization of on-target adverse events caused by TRK inhibitor therapy. Ann Oncol. 2020;31(9):1207-1215. doi:10.1016/j.annonc.2020.05.006