Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children

Fusions involving one of three tropomyosin receptor kinases (TRK) are represented in various pediatric and adult cancers, prompting a series of prospective studies designed around the TRK inhibitor larotrectinib.

Fusions involving one of three tropomyosin receptor kinases (TRK) are represented in various pediatric and adult cancers, prompting a series of prospective studies designed around the TRK inhibitor larotrectinib. A Phase I trial was limited to adult patients with TRK fusion-positive disease, a Phase I–II study looked exclusively at children, and a Phase II investigation focused on both populations. The main endpoint for the combined analysis was overall response rate, based on independent review, which came in at 75%. Researchers observed a durable response regardless of patient age—which ranged from 4 months to 76 years—or tumor type, of which there were 17 different manifestations. With most adverse events categorized as grade 1 and none of the 55 patients dropping out due to poor outcomes tied to the study drug, the safety profile supports long-term administration. To identify patients who might benefit from larotrectinib, however, advanced screening strategies that can distinguish TRK fusions are needed.