Long-Term Tumor Stability After First-Line Treatment With Larotrectinib in an Infant With NTRK2 Fusion–Positive High-Grade Glioma
Search for other papers by Jillian Simoneau in
Current site
Google Scholar
PubMed
Search for other papers by Patricia Robertson in
Current site
Google Scholar
PubMed
Search for other papers by Karin Muraszko in
Current site
Google Scholar
PubMed
Search for other papers by Cormac O. Maher in
Current site
Google Scholar
PubMed
Search for other papers by Hugh Garton in
Current site
Google Scholar
PubMed
Search for other papers by Rebecca Calvert in
Current site
Google Scholar
PubMed
Search for other papers by Carl Koschmann in
Current site
Google Scholar
PubMed
Search for other papers by Santhosh A. Upadhyaya in
Current site
Google Scholar
PubMed
Search for other papers by Rajen Mody in
Current site
Google Scholar
PubMed
Search for other papers by Noah Brown in
Current site
Google Scholar
PubMed
Search for other papers by Chandan Kumar-Sinha in
Current site
Google Scholar
PubMed
Search for other papers by Hemant Parmar in
Current site
Google Scholar
PubMed
Search for other papers by Sandra Camelo-Piragua in
Current site
Google Scholar
PubMed
Search for other papers by Andrea T. Franson in
Current site
Google Scholar
PubMed
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.
Submitted November 3, 2023; final revision received May 7, 2024; accepted for publication June 4, 2024.
Disclosures: Dr. Franson has disclosed serving on an advisory board for Bayer. The remaining authors have disclosed not having any financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.
© 2019-2024 National Comprehensive Cancer Network