Initial US Approval
20191,2
Indications
The treatment of adult and pediatric patients 12 years of age and older 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
Entrectinib: Recommended Dose/Route
Entrectinib: Dose Reductions for Adverse Reactions
Pivotal Studies1,2
ALKA, STARTRK-1 (NCT02097810) and STARTRK-2 (NCT02568267)
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
Safety
The most common adverse reactions (≥ 20%) include fatigue, constipation, dysgeusia, edema, dizziness, diarrhea, nausea, dysesthesia, dyspnea, myalgia, cognitive impairment, increased weight, cough, vomiting, pyrexia, arthralgia, and vision disorders.The most common laboratory abnormalities (≥ 20%) include increased creatinine, hyperuricemia, increased AST, increased ALT, hypernatremia, hypocalcemia, hypophosphatemia, increased lipase, hypoalbuminemia, increased amylase, hyperkalemia, increased alkaline phosphatase, hyperglycemia, anemia, lymphopenia, neutropenia.1
Dosage Interruption Due to Adverse Events (AEs): 46%1
Permanent Discontinuation Due to AEs: 9%1
References
1. Rozlytrek (Entrectinib) [Package Insert]. Genentech; 2019.
2. Demetri GD, Paz-Ares L, Farago AF, et al. Efficacy and safety of entrectinib in patients with NTRK fusion-positive (NTRK-fp) Tumors: Pooled analysis of STARTRK-2, STARTRK-1 and ALKA-372-001. Annals of Oncology. 2018;29:viii713. doi:10.1093/annonc/mdy424.017