Initial US Approval

  • 20191,2

Indications

  • Adult patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.1
  • Adult and pediatric patients older than 1 month of age with solid tumors that:
    • have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, as detected by an FDA-approved test without a known acquired resistance mutation
    • are metastatic or where surgical resection is likely to result in severe morbidity, and
    • have progressed following treatment or have no satisfactory alternative therapy.
    • This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.1
Entrectinib: Recommended Dose/Route

Entrectinib: Recommended Dose/Route

Entrectinib: Dose Reductions for Adverse Reactions

Entrectinib: Dose Reductions for Adverse Reactions

Pivotal Studies

  • ALKA, STARTRK-1 (NCT02097810) and STARTRK-2 (NCT02568267)1,2
  • Key Inclusion Criteria: Eligible patients were required to have disease progression following systemic therapy or would have required surgery causing significant morbidity for locally advanced disease, measurable disease per RECIST v1.1, at least six months of follow-up after the first dose of entrectinib, and no prior therapy with a tyrosine kinase inhibitor.1,2
  • Treatment: Entrectinib 600 mg (94% of patients) orally once daily until unacceptable toxicity or disease progression.1
Entrectinib: Efficacy Data

Entrectinib: Efficacy Data

Safety

  • Common Adverse Reactions (≥20%): The most frequently reported any grade AEs were fatigue (48%), constipation (46%), dysgeusia (44%), edema (40%), dizziness (38%), diarrhea (35%), nausea (34%), dysesthesia (34%), dyspnea (30%), myalgia (28%), cognitive impairment (27%), increased weight (25%), cough (24%), vomiting (24%), pyrexia (21%), arthralgia (21%), and vision disorders (21%).1
  • Common Laboratory Abnormalities (≥20%): The most frequently reported laboratory abnormalities were increased creatinine (73%), anemia (67%), hyperuricemia (52%), increased AST (44%), lymphopenia (40%), increased ALT (38%), hypernatremia (35%), hypocalcemia (34%), hypophosphatemia (30%), neutropenia (28%), increased lipase (28%), hypoalbuminemia (28%), increased amylase (26%), hyperkalemia (25%), increased alkaline phosphatase (25%), and hyperglycemia (NE).1
  • Dosage Interruption Due to Adverse Events (AEs): 46%1
  • Dosage Reductions Due to AEs: 29%1
  • Permanent Discontinuation Due to AEs: 9%1

References

  1. ROZLYTREK (entrectinib). Prescribing information. Genentech USA, Inc.; 2024. Accessed November 11, 2024. https://www.gene.com/download/pdf/rozlytrek_prescribing.pdf
  2. Doebele RC, Drilon A, Paz-Ares L, et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials. Lancet Oncol. 2020;21(2):271-282. doi: 10.1016/S1470-2045(19)30691-6
  3. Krzakowski MJ, Lu S, Cousin S, et al. Updated analysis of the efficacy and safety of entrectinib in patients (pts) with locally advanced/metastatic NTRK fusion-positive (NTRK-fp) solid tumors. J Clin Oncol.2022;40(16supp):3099. doi: 10.1200/JCO.2022.40.16_suppl.30
  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