Larotrectinib in Pediatric Solid Tumors With TRK Gene Fusions


Key Points

  • Response was observed in 93% of patients with TRK fusions.
  • No responses were observed in patients with TRK fusion–negative patients.

As reported in The Lancet Oncology by Laetsch et al, phase I results from an ongoing phase I/II trial have shown activity of the TRK kinase inhibitor larotrectinib in pediatric patients with solid tumors harboring TRK fusions.

Study Details

In the study, 24 patients in a dose-escalation cohort with a median age of 4.5 years were enrolled at 8 U.S. sites between December 2015 and April 2017 and received oral larotrectinib (capsule or liquid formulation) twice daily on a continuous 28-day schedule in increasing doses adjusted for age and body weight. Of the 24 patients, 17 had tumors with TRK fusions. Patients had locally advanced or metastatic solid tumors, or central nervous system tumors that had relapsed, progressed, or were nonresponsive to available therapies. Among patients with TRK fusion–positive cancers, 8 (47%) had infantile fibrosarcoma, 7 (41%) had other soft-tissue sarcomas, and 2 (12%) had papillary thyroid cancer.


Median follow-up was 5.6 months. Objective response was observed in 14 (93%) of 15 evaluable patients with TRK fusion–positive cancers on RECISTv1.1 criteria, with the remaining patient showing tumor regression. Median duration of response was not reached. Response was not observed in any of the 7 evaluable patients without TRK fusions.


The most common treatment-related adverse events of any grade were increased ALT and AST (42% each), leukopenia (21%), decreased neutrophil count (21%), and vomiting (21%). Grade 3 ALT elevation was the only dose-limiting toxicity, observed in one patient with progressive disease and no TRK fusion. No grade ≥ 4 treatment-related adverse events were observed. Serious treatment-related adverse events consisted of grade 3 nausea and grade 3 ejection fraction decrease in two patients on anthracycline treatment during 28-day follow-up after discontinuing larotrectinib. The maximum tolerated dose was not reached; 100 mg/m2 (maximum of 100 mg per dose) was established as the recommended phase II dose.

The investigators concluded, “The TRK inhibitor larotrectinib was well tolerated in pediatric patients and showed encouraging antitumour activity in all patients with TRK fusion–positive tumors. The recommended phase II dose was defined as 100 mg/m2 (maximum 100 mg per dose) for infants, children, and adolescents, regardless of age.”

The study was funded by Loxo Oncology Inc.

Theodore W. Laetsch, MD, of the Department of Pediatrics, University of Texas Southwestern Medical Center, is the corresponding author for The Lancet Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.