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

   


Authors: Doz, F.; van Tilburg, C. M.; Geoerger, B.; Højgaard, M.; Øra, I.; Boni, V.; Capra, M.; Chisholm, J.; Chung, H. C.; DuBois, S. G.; Gallego-Melcon, S.; Gerber, N. U.; Goto, H.; Grilley-Olson, J. E.; Hansford, J. R.; Hong, D. S.; Italiano, A.; Kang, H. J.; Nysom, K.; Thorwarth, A.; Stefanowicz, J.; Tahara, M.; Ziegler, D. S.; Gavrilovic, I. T.; Norenberg, R.; Dima, L.; De La Cuesta, E.; Laetsch, T. W.; Drilon, A.; Perreault, S.
Article Title: Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors
Abstract: 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.
Keywords: mutation; pain; classification; receptor gene; solid tumors; response assessment; criteria; congenital; insensitivity; larotrectinib; ntrk gene fusions; trk fusion; primary cns tumors; grade glioma recommendations
Journal Title: Neuro-Oncology
Volume: 24
Issue: 6
ISSN: 1522-8517
Publisher: Oxford University Press  
Date Published: 2022-06-01
Start Page: 997
End Page: 1007
Language: English
ACCESSION: WOS:000764797100001
DOI: 10.1093/neuonc/noab274
PROVIDER: wos
PMCID: PMC9159442
PUBMED: 34850167
Notes: Article -- Source: Wos
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MSK Authors
  1. Igor T Gavrilovic
    73 Gavrilovic
  2. Alexander Edward Drilon
    632 Drilon
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