Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG)

BACKGROUND: Entrectinib is a TRKA/B/C, ROS1, ALK tyrosine kinase inhibitor approved for the treatment of adults and children aged ≥12 years with NTRK fusion-positive solid tumors and adults with ROS1 fusion-positive non–small-cell lung cancer. We report an analysis of the STARTRK-NG trial, investiga...

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Autores principales: Desai, Ami V, Robinson, Giles W, Gauvain, Karen, Basu, Ellen M, Macy, Margaret E, Maese, Luke, Whipple, Nicholas S, Sabnis, Amit J, Foster, Jennifer H, Shusterman, Suzanne, Yoon, Janet, Weiss, Brian D, Abdelbaki, Mohamed S, Armstrong, Amy E, Cash, Thomas, Pratilas, Christine A, Corradini, Nadège, Marshall, Lynley V, Farid-Kapadia, Mufiza, Chohan, Saibah, Devlin, Clare, Meneses-Lorente, Georgina, Cardenas, Alison, Hutchinson, Katherine E, Bergthold, Guillaume, Caron, Hubert, Chow Maneval, Edna, Gajjar, Amar, Fox, Elizabeth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9527518/
https://www.ncbi.nlm.nih.gov/pubmed/35395680
http://dx.doi.org/10.1093/neuonc/noac087
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author Desai, Ami V
Robinson, Giles W
Gauvain, Karen
Basu, Ellen M
Macy, Margaret E
Maese, Luke
Whipple, Nicholas S
Sabnis, Amit J
Foster, Jennifer H
Shusterman, Suzanne
Yoon, Janet
Weiss, Brian D
Abdelbaki, Mohamed S
Armstrong, Amy E
Cash, Thomas
Pratilas, Christine A
Corradini, Nadège
Marshall, Lynley V
Farid-Kapadia, Mufiza
Chohan, Saibah
Devlin, Clare
Meneses-Lorente, Georgina
Cardenas, Alison
Hutchinson, Katherine E
Bergthold, Guillaume
Caron, Hubert
Chow Maneval, Edna
Gajjar, Amar
Fox, Elizabeth
author_facet Desai, Ami V
Robinson, Giles W
Gauvain, Karen
Basu, Ellen M
Macy, Margaret E
Maese, Luke
Whipple, Nicholas S
Sabnis, Amit J
Foster, Jennifer H
Shusterman, Suzanne
Yoon, Janet
Weiss, Brian D
Abdelbaki, Mohamed S
Armstrong, Amy E
Cash, Thomas
Pratilas, Christine A
Corradini, Nadège
Marshall, Lynley V
Farid-Kapadia, Mufiza
Chohan, Saibah
Devlin, Clare
Meneses-Lorente, Georgina
Cardenas, Alison
Hutchinson, Katherine E
Bergthold, Guillaume
Caron, Hubert
Chow Maneval, Edna
Gajjar, Amar
Fox, Elizabeth
author_sort Desai, Ami V
collection PubMed
description BACKGROUND: Entrectinib is a TRKA/B/C, ROS1, ALK tyrosine kinase inhibitor approved for the treatment of adults and children aged ≥12 years with NTRK fusion-positive solid tumors and adults with ROS1 fusion-positive non–small-cell lung cancer. We report an analysis of the STARTRK-NG trial, investigating the recommended phase 2 dose (RP2D) and activity of entrectinib in pediatric patients with solid tumors including primary central nervous system tumors. METHODS: STARTRK-NG (NCT02650401) is a phase 1/2 trial. Phase 1, dose-escalation of oral, once-daily entrectinib, enrolled patients aged <22 years with solid tumors with/without target NTRK1/2/3, ROS1, or ALK fusions. Phase 2, basket trial at the RP2D, enrolled patients with intracranial or extracranial solid tumors harboring target fusions or neuroblastoma. Primary endpoints: phase 1, RP2D based on toxicity; phase 2, objective response rate (ORR) in patients harboring target fusions. Safety-evaluable patients: ≥1 dose of entrectinib; response-evaluable patients: measurable/evaluable baseline disease and ≥1 dose at RP2D. RESULTS: At data cutoff, 43 patients, median age of 7 years, were response-evaluable. In phase 1, 4 patients experienced dose-limiting toxicities. The most common treatment-related adverse event was weight gain (48.8%). Nine patients experienced bone fractures (20.9%). In patients with fusion-positive tumors, ORR was 57.7% (95% CI 36.9-76.7), median duration of response was not reached, and median (interquartile range) duration of treatment was 10.6 months (4.2-18.4). CONCLUSIONS: Entrectinib resulted in rapid and durable responses in pediatric patients with solid tumors harboring NTRK1/2/3 or ROS1 fusions.
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spelling pubmed-95275182022-10-03 Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG) Desai, Ami V Robinson, Giles W Gauvain, Karen Basu, Ellen M Macy, Margaret E Maese, Luke Whipple, Nicholas S Sabnis, Amit J Foster, Jennifer H Shusterman, Suzanne Yoon, Janet Weiss, Brian D Abdelbaki, Mohamed S Armstrong, Amy E Cash, Thomas Pratilas, Christine A Corradini, Nadège Marshall, Lynley V Farid-Kapadia, Mufiza Chohan, Saibah Devlin, Clare Meneses-Lorente, Georgina Cardenas, Alison Hutchinson, Katherine E Bergthold, Guillaume Caron, Hubert Chow Maneval, Edna Gajjar, Amar Fox, Elizabeth Neuro Oncol Pediatric Neuro-Oncology BACKGROUND: Entrectinib is a TRKA/B/C, ROS1, ALK tyrosine kinase inhibitor approved for the treatment of adults and children aged ≥12 years with NTRK fusion-positive solid tumors and adults with ROS1 fusion-positive non–small-cell lung cancer. We report an analysis of the STARTRK-NG trial, investigating the recommended phase 2 dose (RP2D) and activity of entrectinib in pediatric patients with solid tumors including primary central nervous system tumors. METHODS: STARTRK-NG (NCT02650401) is a phase 1/2 trial. Phase 1, dose-escalation of oral, once-daily entrectinib, enrolled patients aged <22 years with solid tumors with/without target NTRK1/2/3, ROS1, or ALK fusions. Phase 2, basket trial at the RP2D, enrolled patients with intracranial or extracranial solid tumors harboring target fusions or neuroblastoma. Primary endpoints: phase 1, RP2D based on toxicity; phase 2, objective response rate (ORR) in patients harboring target fusions. Safety-evaluable patients: ≥1 dose of entrectinib; response-evaluable patients: measurable/evaluable baseline disease and ≥1 dose at RP2D. RESULTS: At data cutoff, 43 patients, median age of 7 years, were response-evaluable. In phase 1, 4 patients experienced dose-limiting toxicities. The most common treatment-related adverse event was weight gain (48.8%). Nine patients experienced bone fractures (20.9%). In patients with fusion-positive tumors, ORR was 57.7% (95% CI 36.9-76.7), median duration of response was not reached, and median (interquartile range) duration of treatment was 10.6 months (4.2-18.4). CONCLUSIONS: Entrectinib resulted in rapid and durable responses in pediatric patients with solid tumors harboring NTRK1/2/3 or ROS1 fusions. Oxford University Press 2022-04-08 /pmc/articles/PMC9527518/ /pubmed/35395680 http://dx.doi.org/10.1093/neuonc/noac087 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Pediatric Neuro-Oncology
Desai, Ami V
Robinson, Giles W
Gauvain, Karen
Basu, Ellen M
Macy, Margaret E
Maese, Luke
Whipple, Nicholas S
Sabnis, Amit J
Foster, Jennifer H
Shusterman, Suzanne
Yoon, Janet
Weiss, Brian D
Abdelbaki, Mohamed S
Armstrong, Amy E
Cash, Thomas
Pratilas, Christine A
Corradini, Nadège
Marshall, Lynley V
Farid-Kapadia, Mufiza
Chohan, Saibah
Devlin, Clare
Meneses-Lorente, Georgina
Cardenas, Alison
Hutchinson, Katherine E
Bergthold, Guillaume
Caron, Hubert
Chow Maneval, Edna
Gajjar, Amar
Fox, Elizabeth
Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG)
title Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG)
title_full Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG)
title_fullStr Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG)
title_full_unstemmed Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG)
title_short Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG)
title_sort entrectinib in children and young adults with solid or primary cns tumors harboring ntrk, ros1, or alk aberrations (startrk-ng)
topic Pediatric Neuro-Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9527518/
https://www.ncbi.nlm.nih.gov/pubmed/35395680
http://dx.doi.org/10.1093/neuonc/noac087
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