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Beyond Clinical Trials: Understanding Neurotrophic Tropomyosin Receptor Kinase Inhibitor Challenges and Efficacy in
Carolina Sgarioni Camargo Vince1,2, Maria Sol Brassesco3, Bruna Minniti Mançano4
1Childhood Cancer Treatment Institute (ITACI), São Paulo Medical School, University of São Paulo, São Paulo, Brazil.
Purpose:
Our study aimed to explore real-world treatment scenarios for children and adolescents with neurotrophic tropomyosin receptor kinase (NTRK)-fused tumors, emphasizing access, responses, side effects, and outcomes.
Patients And Methods:
Pooled clinical data from 17 pediatric cases (11 soft-tissue sarcomas, five brain tumors, and one neuroblastoma) treated with larotrectinib and radiologic images for 14 patients were centrally reviewed. Testing for gene fusions was prompted by poor response to treatment, tumor progression, or aggressiveness.
Results:
Six different NTRK fusion subtypes were detected, and various payment sources for testing and medication were reported. Radiologic review revealed objective tumor responses (OR) in 11 of 14 patients: Complete responses: two; partial responses: nine; and stable disease: three cases. Grades 1 or 2 Common Terminology Criteria for Adverse Events adverse effects were reported in five patients. Regarding the entire cohort's clinical information, 15 of 17 patients remain alive (median observation time: 25 months): four with no evidence of disease and 11 alive with disease (10 without progression). One patient developed resistance to the NTRK inhibitor and died from disease progression while another patient died due to an unrelated cause.
Conclusion:
This real-world study confirms favorable agnostic tumor OR rates to larotrectinib in children with NTRK-fused tumors. Better coordination to facilitate access to medication remains a challenge, particularly in middle-income countries like Brazil.
Insights
Larotrectinib shows favorable objective tumor response rates in children with neurotrophic tropomyosin receptor kinase (NTRK)-fused tumors. However, challenges in medication access persist, especially in middle-income nations.
Area of Science:
- Pediatric Oncology
- Molecular Diagnostics
- Cancer Therapeutics
Background:
- Neurotrophic tropomyosin receptor kinase (NTRK)-fused tumors are rare in children and adolescents.
- Real-world data on larotrectinib treatment in this population are limited.
- Understanding treatment access and outcomes is crucial for optimizing care.
Purpose of the Study:
- To evaluate real-world treatment scenarios for pediatric patients with NTRK-fused tumors.
- To assess larotrectinib's efficacy, safety, and accessibility in this cohort.
- To identify challenges in accessing targeted therapy for rare pediatric cancers.
Main Methods:
- Pooled clinical data from 17 pediatric patients treated with larotrectinib were analyzed.
- Radiologic images from 14 patients were centrally reviewed for tumor response.
- Gene fusion testing was performed based on clinical presentation and treatment response.
Main Results:
- Objective tumor response (OR) was observed in 11 of 14 patients (complete response: 2; partial response: 9).
- 15 of 17 patients remained alive at a median follow-up of 25 months.
- Adverse events were generally low-grade (Grades 1-2), reported in five patients.
Conclusions:
- Larotrectinib demonstrates favorable agnostic tumor response rates in children with NTRK-fused tumors.
- Facilitating medication access, particularly in middle-income countries, remains a significant challenge.
- Real-world evidence supports larotrectinib's role in treating NTRK-fusion-positive pediatric cancers.
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