Precision oncology in practice: real-world experience of larotrectinib in pediatric extracranial NTRK fusion-positive solid tumors: a Turkish Pediatric Oncology Group (TPOG) report

Background 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 efficacy and a favorable safety profile in clinical trials. However, real-world data remain limited. We report a national multicenter experience evaluating outcomes of pediatric patients with extracranial NTRK fusion–positive tumors treated with larotrectinib in Türkiye. Methods This retrospective, descriptive multicenter study included pediatric patients with solid tumors harboring NTRK gene fusions, treated with larotrectinib in 15 centers between August 2023-April 2025. Treatment response (RECIST v1.1), adverse events (CTCAE v5.0) and survival outcomes were analyzed. Results Twenty-one patients (57% female) were included; median age at diagnosis was 3 months (1 day – 182 months). Infantile fibrosarcoma (IFS) was the most common diagnosis (n= 15), followed by rhabdomyosarcoma (RMS), epithelioid sarcoma (ES), and desmoplastic small round cell tumor (DSRCT). Six had metastasis at diagnosis. Larotrectinib was initiated due to disease progression/inadequate response to prior therapy (81%), treatment-related toxicity (14.3%), and as maintenance therapy in one patient (4.8%). Among 15 patients with infantile fibrosarcoma, the objective response rate was 93.3% (14/15). Among the six patients with non-IFS tumors, five patients, all of whom had received larotrectinib after several lines of systemic treatment, experienced disease progression and subsequently died. One patient with a NTRK-rearranged undifferentiated spindle cell neoplasm of the soft tissue maintained a continued complete response and remained disease-free for 5.5 years since initial diagnosis. No treatment-limiting adverse events were observed. Conclusions In this national real-world cohort, larotrectinib showed substantial clinical activity in pediatric patients with NTRK fusion-positive tumors, particularly in IFS, with favorable tolerability. 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. *Larotrectinib was provided through the early access to medicines program for humanitarian purposes and the data reflects real world data and does not reflect phase research data. The pharmaceutical company did not provide any kind of support in the planning/reporting/publication of the study.