BACKGROUND: The highly selective oral tropomyosin receptor kinase (TRK) 
inhibitor larotrectinib has demonstrated significant activity in adult and 
pediatric TRK fusion cancers. In the current study, the authors describe the 
clinical course of children with locally advanced TRK fusion sarcoma who were 
treated preoperatively with larotrectinib and underwent subsequent surgical 
resection.
METHODS: A total of 24 children were treated on a pediatric phase 1 trial of 
larotrectinib (ClinicalTrials.gov identifier NCT02637687). Five children who had 
a documented TRK fusion sarcoma and underwent surgical resection were included 
in the current analysis. Tumor response (Response Evaluation Criteria In Solid 
Tumors [RECIST] version 1.1) and surgical outcomes were collected prospectively.
RESULTS: A total of 5 patients (median age, 2 years; range, 0.4-12 years) had 
locally advanced infantile fibrosarcoma (3 patients) or soft-tissue sarcoma (2 
patients). Four patients had disease that was refractory to standard therapy. 
All 5 patients achieved a partial response to larotrectinib by version 1.1 of 
RECIST and underwent surgical resection after a median of 6 cycles (range, 4-9 
cycles) of treatment. Surgical resections were R0 (negative resection margins 
with no tumor at the inked resection margin) in 3 patients, R1 (microscopic 
residual tumor at the resection margin) in 1 patient, and R2 (macroscopic 
residual tumor at the resection margin) in 1 patient. Three patients achieved 
complete (2 patients) or near-complete (>98% treatment effect; 1 patient) 
pathologic responses. These patients remained in follow-up and were no longer 
receiving larotrectinib for a minimum of 7 to 15 months postoperatively. Two 
patients had viable tumor at the time of surgical resection and positive 
resection margins and continued to receive adjuvant larotrectinib. No patients 
experienced postoperative complications or wound healing issues.
CONCLUSIONS: Children with locally advanced TRK fusion sarcomas may proceed to 
surgical resection after treatment with the selective TRK inhibitor 
larotrectinib, thereby sparing them the potentially significant morbidity noted 
with current approaches. These results support the evaluation of larotrectinib 
as presurgical therapy in children with newly diagnosed TRK fusion sarcomas.