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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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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. |
format | Online Article Text |
id | pubmed-9527518 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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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