Study findings show that long-term larotrectinib therapy is feasible for use in the treatment of pediatric and adult patients with advanced TRK fusion–positive solid tumors (Lancet Oncol. 2020 Feb 24. Epub ahead of print).

“The selective TRK inhibitor larotrectinib was approved for paediatric and adult patients with advanced TRK fusion-positive solid tumours based on a primary analysis set of 55 patients. The aim of our analysis was to explore the efficacy and long-term safety of larotrectinib in a larger population of patients with TRK fusion-positive solid tumours,” explained David S. Hong, MD, University of Texas MD Anderson Cancer Center, Houston, and colleagues.

Overall, 159 patients with TRK fusion–positive cancer were enrolled in a phase 1 adult, a phase 1/2 pediatric, or a phase 2 adolescent and adult trial. Although eligibility criteria differed across the 3 studies, patients were eligible for inclusion in the pooled analysis by Dr Hong et al if they were aged ≥1 month; had locally advanced or metastatic non-CNS primary, TRK fusion-positive solid tumor; and (if available) had received previous standard therapy.

“This analysis set includes the 55 patients on which approval of larotrectinib was based,” the investigators said.

Patients were given larotrectinib continuously in a 28-day schedule, with most adults receiving 100 mg twice daily and pediatric patients given 100 mg/m² (maximum of 100 mg) twice daily.

The main end point was objective response as evaluated in an intention-to-treat analysis by local investigators.

Among 153 evaluable patients, 121 (79%) had an objective response as per investigator assessment (95% CI, 72-85), with 24 (16%) having complete responses.

Of 260 patients in a safety population who were treated regardless of TRK fusion status, the most frequently reported grade 3 or 4 adverse events related to larotrectinib therapy were increased alanine aminotransferase (3%), anemia (2%), and decreased neutrophil count (2%).

The most common serious adverse events associated with larotrectinib were increased alanine aminotransferase, increased aspartate aminotransferase, and nausea, each occurring in <1% of patients.

There were no treatment-related deaths reported.

“These data confirm that TRK fusions define a unique molecular subgroup of advanced solid tumours for which larotrectinib is highly active,” Dr Hong and colleagues said.

“Safety data indicate that long-term administration of larotrectinib is feasible,” they concluded.—Hina Porcelli