Real-world experience of larotrectinib in children, adolescents and young adultes with TRK fusion solid tumors: the Sacha-France experience
Menée en France à partir de données de vie réelle portant sur 25 enfants, adolescents et jeunes adultes atteints d'une tumeur solide avec fusion du gène TRK (âge médian : 2,8 ans), cette étude prospective évalue l'efficacité, du point de vue du taux de réponse globale, de la survie sans événement et de la survie globale, et la toxicité du larotrectinib
Background: Larotrectinib is a selective tropomyosin receptor kinase (TRK) inhibitor approved for the treatment of NTRK fusion–positive tumors. Although its efficacy has been demonstrated in clinical trials, particularly in infantile fibrosarcoma (IFS), real-world data in pediatric populations remain limited.
Methods: We conducted a prospective observational study within the SACHA- France study, including patients <25 years treated with larotrectinib outside clinical trials between April 2019 and September 2025. Clinical characteristics, molecular data, treatment indications, responses, survival outcomes, toxicity, treatment discontinuation, and resistance were analyzed.
Results: Twenty-five patients were included (median age 2.8 years): IFS (n=9), extra-CNS tumors (n=10) and CNS tumors (n=6). Twelve patients were treated at progression, nine to avoid mutilating surgery, two for multifocal/metastatic disease, and two as maintenance for high relapse risk; five received upfront larotrectinib. The overall response rate was 70% (95% CI: 47–87), with a median time to best response of 2 months. Two-year event-free and overall survival rates were 61.3% (95% CI: 38.3-77.7) and 74.9% (95% CI: 52.4-87.9) respectively. A trend toward higher 2-year EFS was observed in IFS versus CNS tumors (72.9% [95% CI: 26.7–92.9] vs 33% [95% CI: 10.5–80]). Treatment-related adverse events were reported in 8% of patients. Disease progression occurred in five patients, with acquired resistance mutations in the kinase domain confirmed in two.
Conclusion: Larotrectinib shows meaningful efficacy and favorable tolerance across NTRK fusion–positive malignancies beyond IFS. These real-world data support early molecular testing, highlight histology-dependent outcomes, and inform clinical management strategies.
European Journal of Cancer , résumé, 2026