1. Beyond Clinical Trials: Understanding Neurotrophic Tropomyosin Receptor Kinase Inhibitor Challenges and Efficacy in Real-World Pediatric Oncology.
- Author
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Vince CSC, Brassesco MS, Mançano BM, Gregianin LJ, Carbone EK, do Amaral E Castro A, Dwan VSY, Menezes da Silva RZ, Mariano CS, da Mata JF, Silva MO, Caran EMM, Macedo CD, Alves da Costa G, Esteves TC, Silva LN, Ferman SE, Martins FD, Cristófani LM, Odone-Filho V, Silva MM, Reis RM, Pianovski MAD, Campregher PV, Kunii MS, de Sá Rodrigues KE, Carvalho Filho NP, and Valera ET
- Subjects
- Humans, Child, Male, Female, Adolescent, Child, Preschool, Pyrimidines therapeutic use, Receptor, trkA genetics, Receptor, trkA antagonists & inhibitors, Brain Neoplasms drug therapy, Brain Neoplasms genetics, Sarcoma drug therapy, Sarcoma genetics, Neuroblastoma drug therapy, Neuroblastoma genetics, Infant, Receptor, trkB genetics, Receptor, trkC genetics, Clinical Trials as Topic, Pyrazoles therapeutic use, Protein Kinase Inhibitors therapeutic use
- Abstract
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.
- Published
- 2024
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