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 Thorwarth; Joanna Stefanowicz; Makoto Tahara; David S Ziegler; Igor T Gavrilovic; Ricarda Norenberg; Laura Dima; Esther De La Cuesta; Theodore W Laetsch; Alexander Drilon; Sebastien Perreault

doi:10.1093/neuonc/noab274

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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	997-1007
Journal	Neuro-Oncology
Volume	24
Issue number	6
Early online date	2021
DOIs	https://doi.org/10.1093/neuonc/noab274
Publication status	Published - 2022
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1093/neuonc/noab274Licence: CC BY

Cite this

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., ... Perreault, S. (2022). Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors. Neuro-Oncology, 24(6), 997-1007. https://doi.org/10.1093/neuonc/noab274

@article{90f8543cbd7d4f348ed913248418fe15,

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. 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.",

author = "Fran{\c c}ois Doz and {van Tilburg}, {Cornelis M} and Birgit Geoerger and Martin H{\o}jgaard and Ingrid {\O}ra and Valentina Boni and Michael Capra and Julia Chisholm and Chung, {Hyun Cheol} and DuBois, {Steven G} and Soledad Gallego-Melcon and Gerber, {Nicolas U} and Hiroaki Goto and Grilley-Olson, {Juneko E} and Hansford, {Jordan R} and Hong, {David S} and Antoine Italiano and Kang, {Hyoung Jin} and Karsten Nysom and Anne Thorwarth and Joanna Stefanowicz and Makoto Tahara and Ziegler, {David S} and Gavrilovic, {Igor T} and Ricarda Norenberg and Laura Dima and {De La Cuesta}, Esther and Laetsch, {Theodore W} and Alexander Drilon and Sebastien Perreault",

note = "{\textcopyright} The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.",

year = "2022",

doi = "10.1093/neuonc/noab274",

language = "English",

volume = "24",

pages = "997--1007",

journal = "Neuro-Oncology",

issn = "1523-5866",

publisher = "Oxford University Press",

number = "6",

}

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 2022, 'Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors', Neuro-Oncology, vol. 24, no. 6, pp. 997-1007. https://doi.org/10.1093/neuonc/noab274

TY - JOUR

T1 - Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors

AU - Doz, François

AU - van Tilburg, Cornelis M

AU - Geoerger, Birgit

AU - Højgaard, Martin

AU - Øra, Ingrid

AU - Boni, Valentina

AU - Capra, Michael

AU - Chisholm, Julia

AU - Chung, Hyun Cheol

AU - DuBois, Steven G

AU - Gallego-Melcon, Soledad

AU - Gerber, Nicolas U

AU - Goto, Hiroaki

AU - Grilley-Olson, Juneko E

AU - Hansford, Jordan R

AU - Hong, David S

AU - Italiano, Antoine

AU - Kang, Hyoung Jin

AU - Nysom, Karsten

AU - Thorwarth, Anne

AU - Stefanowicz, Joanna

AU - Tahara, Makoto

AU - Ziegler, David S

AU - Gavrilovic, Igor T

AU - Norenberg, Ricarda

AU - Dima, Laura

AU - De La Cuesta, Esther

AU - Laetsch, Theodore W

AU - Drilon, Alexander

AU - Perreault, Sebastien

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

U2 - 10.1093/neuonc/noab274

DO - 10.1093/neuonc/noab274

M3 - Article

C2 - 34850167

SN - 1523-5866

VL - 24

SP - 997

EP - 1007

JO - Neuro-Oncology

JF - Neuro-Oncology

IS - 6

ER -

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

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this