Larotrectinib

Larotrectinib is a selective oral inhibitor of tropomyosin receptor kinase (TRK) receptors TRKA, TRKB, and TRKC. It targets tumors driven by NTRK gene fusions, which create constitutively active TRK signaling that can promote tumor growth. By blocking TRK signaling, larotrectinib can induce tumor responses across multiple cancer types, regardless of tissue origin.

Indications and regulatory status: Larotrectinib is approved for solid tumors that harbor an NTRK gene fusion and for which there is no satisfactory alternative treatment or no known resistance mechanism. It has been marketed under the brand name Vitrakvi and was among the first medicines approved in a tissue-agnostic approach by major regulatory authorities, including the U.S. FDA.

Efficacy: In pediatric and adult trials, larotrectinib produced notable objective response rates across a variety of tumor histologies, with many patients experiencing tumor shrinkage. Responses have been durable in a substantial subset of patients, contributing to meaningful disease control for extended periods in some cases.

Administration and safety: Larotrectinib is taken orally, typically in capsule form. The treatment is generally well tolerated, with common adverse effects including fatigue, nausea, vomiting, dizziness, and transient increases in liver enzymes. Serious adverse events are uncommon but ongoing monitoring for hepatic function and blood counts is advisable. Dose adjustments may be needed for drug interactions or hepatic impairment.

History and development: Larotrectinib was developed by Loxo Oncology and later approved by regulatory agencies as a tissue-agnostic therapy for NTRK fusion–positive cancers. It is one of several TRK inhibitors used to treat tumors driven by NTRK fusions.