Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors
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Author
Doz, F
van Tilburg, CM
Geoerger, B
Højgaard, M
Øra, I
Boni, V
Capra, M
Chisholm, J
Chung, HC
DuBois, SG
Gallego-Melcon, S
Gerber, NU
Goto, H
Grilley-Olson, JE
Hansford, JR
Hong, DS
Italiano, A
Kang, HJ
Nysom, K
Thorwarth, A
Stefanowicz, J
Tahara, M
Ziegler, DS
Gavrilovic, IT
Norenberg, R
Dima, L
De La Cuesta, E
Laetsch, TW
Drilon, A
Perreault, S
Type
Journal Article
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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. 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.
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Research team
Sarcoma Clinical Trials in children and young people
Language
eng
Date accepted
2021-11-27
Citation
Neuro-Oncology
Publisher
Oxford University Press (OUP)