Precision oncology in practice: real-world multicenter experience with larotrectinib in pediatric extracranial NTRK fusion-positive tumors

Abstract

Gene fusions involving NTRK1/2/3 represent actionable oncogenic drivers across a spectrum of rare pediatric solid tumors. Larotrectinib, a highly selective TRK inhibitor, has demonstrated robust efficacy and a favorable safety profile in clinical trials. However, real-world data from middle-income countries remain limited. We report a national multicenter real-world experience evaluating outcomes of pediatric patients with NTRK fusion–positive tumors treated with larotrectinib in Türkiye. Methods: This retrospective, descriptive multicenter study included pediatric patients (0–18 years) with histologically confirmed solid tumors harboring NTRK gene fusions, treated with larotrectinib for ≥1 month between August 2023 and April 2025. Clinical data were collected from 15 tertiary pediatric oncology centers. Treatment response was assessed using RECIST v1.1 or tumor-specific pediatric criteria. Adverse events were graded per CTCAE v5.0. Survival outcomes were analyzed descriptively. Results: Twenty-two patients were included; median age at diagnosis was 3 months (range, 1 day–182 months), and 59% were female. Infantile fibrosarcoma (IFS) was the most common diagnosis (n=16, 72.7%), followed by rhabdomyosarcoma (RMS), epithelioid sarcoma (ES), desmoplastic small round cell tumor (DSRCT). Six patients (27.3%) had metastatic disease at diagnosis. Larotrectinib was initiated due to disease progression or inadequate response to prior therapy in 86% of patients, treatment-related toxicity in 9%, and as maintenance therapy in one patient. After a median follow-up of 24 months, 10 patients achieved complete response, 6 had partial response or stable disease, and 4 experienced progression; 3 patients later relapsed. One patient died due to progressive disease. The 24-month overall survival rate was 95.5%, and 82% of patients remained event-free. No treatment-limiting adverse events were observed. Conclusions: In this national real-world cohort, larotrectinib demonstrated high efficacy, durable disease control, and an excellent safety profile in pediatric patients with NTRK fusion–positive solid tumors, particularly IFS. These findings support early integration of molecular diagnostics and TRK inhibition into routine pediatric oncology practice and provide valuable real-world evidence from a middle-income country setting.