Initial US Approval

  • 20181,2

Indications

  • Approved for the treatment of adult and pediatric patients with solid tumors that:1
    • 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. 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

Larotrectinib: Dose Reductions for Adverse Reactions

Pivotal Studies

  • LOXO-TRK-14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431)1,3
  • 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

Larotrectinib: Efficacy Data

Safety 

  • Common Adverse Reactions (≥20%): The most frequently reported any grade AEs were musculoskeletal pain (42%), fatigue (36%), cough (32%), constipation (27%), diarrhea (27%), nausea (25%), dizziness, 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 (42%), anemia (42%), hypoalbuminemia (36%), neutropenia (36%), increase alkaline phosphatase (34%), leukopenia (28%), hypocalcemia (25%), lymphopenia (22%).1
  • Dosage Interruption Due to Adverse Events (AEs): 39%1
  • Dosage Reduction Due to AEs: 8%1
  • Permanent Discontinuation Due to AEs: 9%1

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. 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
  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