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Long-Term Tumor Stability After First-Line Treatment With Larotrectinib in an Infant With NTRK2 Fusion-Positive High-Grade Glioma.
Simoneau, Jillian; Robertson, Patricia; Muraszko, Karin; Maher, Cormac O; Garton, Hugh; Calvert, Rebecca; Koschmann, Carl; Upadhyaya, Santhosh A; Mody, Rajen; Brown, Noah; Kumar-Sinha, Chandan; Parmar, Hemant; Camelo-Piragua, Sandra; Franson, Andrea T.
Afiliación
  • Simoneau J; Department of Pediatrics, University of Michigan, Michigan Medicine, Ann Arbor, MI.
  • Robertson P; Department of Pediatrics, University of Michigan, Michigan Medicine, Ann Arbor, MI.
  • Muraszko K; Department of Neurosurgery, University of Michigan, Michigan Medicine, Ann Arbor, MI.
  • Maher CO; Department of Neurosurgery, Stanford University, Stanford, CA.
  • Garton H; Department of Neurosurgery, University of Michigan, Michigan Medicine, Ann Arbor, MI.
  • Calvert R; Department of Pediatrics, University of Michigan, Michigan Medicine, Ann Arbor, MI.
  • Koschmann C; Department of Pediatrics, University of Michigan, Michigan Medicine, Ann Arbor, MI.
  • Upadhyaya SA; Department of Pediatrics, University of Michigan, Michigan Medicine, Ann Arbor, MI.
  • Mody R; Department of Pediatrics, University of Michigan, Michigan Medicine, Ann Arbor, MI.
  • Brown N; Department of Pathology, University of Michigan, Michigan Medicine, Ann Arbor, MI.
  • Kumar-Sinha C; Department of Pathology, University of Michigan, Michigan Medicine, Ann Arbor, MI.
  • Parmar H; Department of Radiology, University of Michigan, Michigan Medicine, Ann Arbor, MI.
  • Camelo-Piragua S; Department of Pathology, University of Michigan, Michigan Medicine, Ann Arbor, MI.
  • Franson AT; Department of Pediatrics, University of Michigan, Michigan Medicine, Ann Arbor, MI.
J Natl Compr Canc Netw ; 22(7)2024 09.
Article en En | MEDLINE | ID: mdl-39236755
ABSTRACT
Tissue-agnostic, molecularly targeted therapies are becoming increasingly common in cancer treatment. The molecular drivers of some classes and subclasses of tumors are rapidly being uncovered in an era of deep tumor sequencing occurring at the time of diagnosis. When and how targeted therapies should fit within up-front cytotoxic chemotherapy and radiation paradigms is yet to be determined, because many of them have been studied in single-arm studies in patients with relapsed or refractory cancer. Infant high-grade gliomas (HGGs) are biologically and clinically distinct from older child and adult HGGs, and are divided into 3 molecular subgroups. Group 1 infant HGGs are driven by receptor tyrosine kinase fusions, most commonly harboring an ALK, ROS1, NTRK, or MET fusion. Both larotrectinib and entrectinib are tropomyosin receptor kinase inhibitors with tissue-agnostic approvals for the treatment of patients with solid tumors harboring an NTRK fusion. This report discusses an 11-month-old female who presented with infantile spasms, found to have an unresectable, NTRK fusion-positive infant HGG. Larotrectinib was prescribed when the NTRK fusion was identified at diagnosis, and without additional intervention to date, the patient has continued with stable disease for >3 years. The only adverse event experienced was grade 1 aspartate transaminase and alanine transaminase elevations. The patient has a normal neurologic examination, is developing age-appropriately in all domains (gross motor, fine motor, cognitive, language, and social-emotional). She is no longer on antiseizure medications. To our knowledge, this is the first report of a patient with an infantile HGG receiving targeted therapy as first-line treatment with prolonged stable disease. A prospective study of larotrectinib in patients with newly diagnosed infant HGG is ongoing, and will hopefully help answer questions about durability of response, the need for additional therapies, and long-term toxicities seen with TRK inhibitors.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirazoles / Pirimidinas / Receptor trkB / Inhibidores de Proteínas Quinasas / Glioma Límite: Female / Humans / Infant Idioma: En Revista: J Natl Compr Canc Netw Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirazoles / Pirimidinas / Receptor trkB / Inhibidores de Proteínas Quinasas / Glioma Límite: Female / Humans / Infant Idioma: En Revista: J Natl Compr Canc Netw Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos