Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors

François Doz, Cornelis M. Van Tilburg, Birgit Geoerger, Martin Højgaard, Ingrid Øra, Valentina Boni, Michael Capra, Julia Chisholm, Hyun Cheol Chung, Steven G. Dubois, Soledad Gallego-Melcon, Nicolas U. Gerber, Hiroaki Goto, Juneko E. Grilley-Olson, Jordan R. Hansford, David S. Hong, Antoine Italiano, Hyoung Jin Kang, Karsten Nysom, Anne ThorwarthJoanna Stefanowicz, Makoto Tahara, David S. Ziegler, Igor T. Gavrilovic, Ricarda Norenberg, Laura Dima, Esther De La Cuesta, Theodore W. Laetsch, Alexander Drilon, Sebastien Perreault

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70 Citations (Scopus)


Background: Larotrectinib is a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor approved to treat adult and pediatric patients with TRK fusion-positive cancer. The aim of this study was to evaluate the efficacy and safety of larotrectinib in patients with TRK fusion-positive primary central nervous system (CNS) tumors. Methods: Patients with TRK fusion-positive primary CNS tumors from two clinical trials (NCT02637687, NCT02576431) were identified. The primary endpoint was investigator-assessed objective response rate (ORR). Results: As of July 2020, 33 patients with TRK fusion-positive CNS tumors were identified (median age: 8.9 years; range: 1.3-79.0). The most common histologies were high-grade glioma (HGG; n = 19) and low-grade glioma (LGG; n = 8). ORR was 30% (95% confidence interval [CI]: 16-49) for all patients. The 24-week disease control rate was 73% (95% CI: 54-87). Twenty-three of 28 patients (82%) with measurable disease had tumor shrinkage. The 12-month rates for duration of response, progression-free survival, and overall survival were 75% (95% CI: 45-100), 56% (95% CI: 38-74), and 85% (95% CI: 71-99), respectively. Median time to response was 1.9 months (range 1.0-3.8 months). Duration of treatment ranged from 1.2-31.3+ months. Treatment-related adverse events were reported for 20 patients, with grade 3-4 in 3 patients. No new safety signals were identified. Conclusions: In patients with TRK fusion-positive CNS tumors, larotrectinib demonstrated rapid and durable responses, high disease control rate, and a favorable safety profile.

Original languageEnglish
Pages (from-to)997-1007
Number of pages11
Issue number6
Publication statusPublished - 2022 Jun 1

Bibliographical note

Publisher Copyright:
© 2021 The Author(s). Published by Oxford University Press on behalf of the Society for Neuro-Oncology.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Clinical Neurology
  • Cancer Research


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