Larotrectinib (Vitrakvi) is a tyrosine kinase receptor (TRK) inhibitor suitable for the treatment of metastatic or unresectable neurotrophic receptor tyrosine kinase (NTRK) gene fusion-positive solid tumors in adults and children.
Patients who were dissatisfied with previous treatment outcomes and had NTRK (1, 2, or 3) gene fusion in tumor sampling could receive lalotinib therapy.
dosage
Lalotinib is available in three doses: 25 mg capsules, 100 mg capsules and 20 mg/ml oral solution. Adults and children with a tumor body surface area (BSA) ≥ 1 m2 should take 100 mg of lalotinib twice daily until the disease progresses or intolerable adverse reactions (AE) develop. Children with tumor surface area ≤ 1 m2 should take 100 mg/m2 of lalotinib twice daily.
FDA approved
Lalotinib is the first drug to receive accelerated approval from the U.S. Food and Drug Administration (FDA) (November 26, 2018) for patients of all ages.
Approval of lalotinib is based on data from three trials, two of which were cohort trials conducted in 2018 (group 1 N=55 and group 2 N=67).
In 24 different types of NTRK fusion-positive tumors, the overall response rate was 81% (63% partial response, 17% complete response). The majority of patients in the primary group (75%) remained disease-free for 1 year after treatment.
AEs and drug interactions
A 2018 study published in the New England Journal of Medicine (NEJM) showed that lalotinib was safe and tolerable, with only 1 in 122 patients discontinuing treatment due to AEs. The most common AEs are fatigue, anemia, elevated liver enzymes, weight gain, and neutropenia. Of the 55 patients in the initial group, only 8 (15%) had their dose reduced due to elevated liver enzymes.
Clinicians should monitor liver tests (ALT and AST) every 2 weeks for the first month of treatment and monthly thereafter. Patients with moderate to severe hepatotoxicity should be treated with half the starting dose.
Patients should avoid strong CYP3A4 inhibitors (eg, clarithromycin, grapefruit juice) while taking lalotinib, or clinicians should reduce the dose of lalotinib by 50% to prevent toxicity. CYP3A4 inducers (e.g., carbamazepine, St. John's wort) may reduce the efficacy of lalotinib. If the use of these drugs cannot be avoided, the clinician should increase the dose of lalotinib by 50%.
Pregnancy/lactation
Lalotinib can cause harm to the fetus and should not be used during pregnancy. Women of childbearing age should use effective contraception during treatment and within 1 week of discontinuation. Clinicians should advise women not to breastfeed during treatment and for 1 week after discontinuation.
summary
Ralotinib is a highly tolerated and potent NTRK gene fusion-positive targeted drug that treats a variety of solid tumors in adults and children.