Larotrectinib Approved to Treat Patients With Advanced Solid Tumors Expressing NTRK

This week, the FDA approved larotrectinib, to be sold as Vitrakvi, for the treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene infusion 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.

This week, the FDA approved larotrectinib, to be sold as Vitrakvi, for the treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene infusion 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.

“Today’s approval marks another step in an important shift toward treating cancers based on their tumor genetics rather than their site of origin in the body,” said FDA Commissioner Scott Gottlieb, MD, in a statement.

Larotrectinib was approved under an accelerated approval pathway based on overall response rate and duration of response. The drug was previously granted breakthrough therapy designation, rare pediatric disease designation, and orphan drug designation. However, “continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.”

The efficacy of larotrectinib was investigated in 3 clinical trials that enrolled 55 pediatric and adult patients. The drug demonstrated a 75% overall response rate across different sold tumor types. Patient responses to the therapy were durable, with 73% of responses lasting at least 6 months and 39% lasting 1 year or more at the time the results were analyzed.

The most common adverse events seen in more than 20% of patients enrolled in the study, regardless of attribution, were increased ALT and AST enzyme blood levels in the liver, anemia, fatigue, nausea, dizziness, cough, vomiting, constipation, and diarrhea.

“The FDA approval of larotrectinib marks an important milestone in how we treat cancers that have an NTRK gene infusion—a rare driver of cancer,” said David Hyman, MD, chief of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center and a global principal investigator for one of the larotrectinib clinical trials. “I have seen firsthand how treatment with larotrectinib, which is designed specifically for this oncogenic driver, can deliver clinically meaningful responses in patients with TRK fusion cancer, regardless of patient age or tumor type.”