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


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


  • larotrectinib
  • NTRK gene fusions
  • primary CNS tumors
  • TRK fusion


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