Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors
(2022) In Neuro-Oncology 24(6). p.997-1007- 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... (More)
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. In 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.
(Less)
- author
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- in
- Neuro-Oncology
- volume
- 24
- issue
- 6
- pages
- 997 - 1007
- publisher
- Oxford University Press
- external identifiers
-
- pmid:34850167
- scopus:85131270788
- ISSN
- 1523-5866
- DOI
- 10.1093/neuonc/noab274
- language
- English
- LU publication?
- no
- additional info
- © The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.
- id
- 90f8543c-bd7d-4f34-8ed9-13248418fe15
- date added to LUP
- 2022-01-26 12:53:03
- date last changed
- 2024-05-03 07:43:23
@article{90f8543c-bd7d-4f34-8ed9-13248418fe15,
abstract = {{<p>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.</p><p>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).</p><p>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. In 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.</p><p>CONCLUSIONS: In patients with TRK fusion-positive CNS tumors, larotrectinib demonstrated rapid and durable responses, high disease control rate, and a favorable safety profile.</p>}},
author = {{Doz, François and van Tilburg, Cornelis M and Geoerger, Birgit and Højgaard, Martin and Øra, Ingrid and Boni, Valentina and Capra, Michael and Chisholm, Julia and Chung, Hyun Cheol and DuBois, Steven G and Gallego-Melcon, Soledad and Gerber, Nicolas U and Goto, Hiroaki and Grilley-Olson, Juneko E and Hansford, Jordan R and Hong, David S and Italiano, Antoine and Kang, Hyoung Jin and Nysom, Karsten and Thorwarth, Anne and Stefanowicz, Joanna and Tahara, Makoto and Ziegler, David S and Gavrilovic, Igor T and Norenberg, Ricarda and Dima, Laura and De La Cuesta, Esther and Laetsch, Theodore W and Drilon, Alexander and Perreault, Sebastien}},
issn = {{1523-5866}},
language = {{eng}},
number = {{6}},
pages = {{997--1007}},
publisher = {{Oxford University Press}},
series = {{Neuro-Oncology}},
title = {{Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors}},
url = {{http://dx.doi.org/10.1093/neuonc/noab274}},
doi = {{10.1093/neuonc/noab274}},
volume = {{24}},
year = {{2022}},
}