Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Pediatric Patients
Neurotrophic tyrosine receptor kinase gene fusions (<i>NTRK</i>) are oncogenic drivers present at a low frequency in most tumour types (<5%), and at a higher frequency (>80%) in a small number of rare tumours (e.g., infantile fibrosarcoma [IFS]) and considered mutually exclusive wi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Current Oncology |
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| Online Access: | https://www.mdpi.com/1718-7729/28/1/38 |
| _version_ | 1797520749853933568 |
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| author | Sébastien Perreault Rose Chami Rebecca J. Deyell Dina El Demellawy Benjamin Ellezam Nada Jabado Daniel A. Morgenstern Aru Narendran Poul H. B. Sorensen Jonathan D. Wasserman Stephen Yip |
| author_facet | Sébastien Perreault Rose Chami Rebecca J. Deyell Dina El Demellawy Benjamin Ellezam Nada Jabado Daniel A. Morgenstern Aru Narendran Poul H. B. Sorensen Jonathan D. Wasserman Stephen Yip |
| author_sort | Sébastien Perreault |
| collection | DOAJ |
| description | Neurotrophic tyrosine receptor kinase gene fusions (<i>NTRK</i>) are oncogenic drivers present at a low frequency in most tumour types (<5%), and at a higher frequency (>80%) in a small number of rare tumours (e.g., infantile fibrosarcoma [IFS]) and considered mutually exclusive with other common oncogenic drivers. Health Canada recently approved two tyrosine receptor kinase (TRK) inhibitors, larotrectinib (for adults and children) and entrectinib (for adults), for the treatment of solid tumours harbouring <i>NTRK</i> gene fusions. In Phase I/II trials, these TRK inhibitors have demonstrated promising overall response rates and tolerability in patients with TRK fusion cancer who have exhausted other treatment options. In these studies, children appear to have similar responses and tolerability to adults. In this report, we provide a Canadian consensus on when and how to test for <i>NTRK</i> gene fusions and when to consider treatment with a TRK inhibitor for pediatric patients with solid tumours. We focus on three pediatric tumour types: non-rhabdomyosarcoma soft tissue sarcoma/unspecified spindle cell tumours including IFS, differentiated thyroid carcinoma, and glioma. We also propose a tumour-agnostic consensus based on the probability of the tumour harbouring an <i>NTRK</i> gene fusion. For children with locally advanced or metastatic TRK fusion cancer who have either failed upfront therapy or lack satisfactory treatment options, TRK inhibitor therapy should be considered. |
| first_indexed | 2024-03-10T08:01:03Z |
| format | Article |
| id | doaj.art-7343ccb0e15c4ebb89b03dcfc1047e22 |
| institution | Directory Open Access Journal |
| issn | 1198-0052 1718-7729 |
| language | English |
| last_indexed | 2024-03-10T08:01:03Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Oncology |
| spelling | doaj.art-7343ccb0e15c4ebb89b03dcfc1047e222023-11-22T11:28:58ZengMDPI AGCurrent Oncology1198-00521718-77292021-01-0128134636610.3390/curroncol28010038Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Pediatric PatientsSébastien Perreault0Rose Chami1Rebecca J. Deyell2Dina El Demellawy3Benjamin Ellezam4Nada Jabado5Daniel A. Morgenstern6Aru Narendran7Poul H. B. Sorensen8Jonathan D. Wasserman9Stephen Yip10Department of Neurosciences, Division of Child Neurology CHU Sainte-Justine, Montreal, QC H3T 1C5, CanadaDepartment of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, CanadaDivision of Pediatric Hematology, Oncology and Bone Marrow Transplant, British Columbia Children’s Hospital and Research Institute, Vancouver, BC V6H 3N1, CanadaPathology Department, Children’s Hospital of Eastern Ontario, Ottawa, ON K1H 8L1, CanadaDepartment of Pathology, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, QC H3T 1C5, CanadaDepartment of Pediatric Hematology-Oncology, MUHC, Montreal, QC H4A 3J1, CanadaDivision of Pediatric Hematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, ON M5G 1X8, CanadaDepartments of Pediatrics, Oncology and, Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, CanadaDivision of Endocrinology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON M5G 1X8, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, CanadaNeurotrophic tyrosine receptor kinase gene fusions (<i>NTRK</i>) are oncogenic drivers present at a low frequency in most tumour types (<5%), and at a higher frequency (>80%) in a small number of rare tumours (e.g., infantile fibrosarcoma [IFS]) and considered mutually exclusive with other common oncogenic drivers. Health Canada recently approved two tyrosine receptor kinase (TRK) inhibitors, larotrectinib (for adults and children) and entrectinib (for adults), for the treatment of solid tumours harbouring <i>NTRK</i> gene fusions. In Phase I/II trials, these TRK inhibitors have demonstrated promising overall response rates and tolerability in patients with TRK fusion cancer who have exhausted other treatment options. In these studies, children appear to have similar responses and tolerability to adults. In this report, we provide a Canadian consensus on when and how to test for <i>NTRK</i> gene fusions and when to consider treatment with a TRK inhibitor for pediatric patients with solid tumours. We focus on three pediatric tumour types: non-rhabdomyosarcoma soft tissue sarcoma/unspecified spindle cell tumours including IFS, differentiated thyroid carcinoma, and glioma. We also propose a tumour-agnostic consensus based on the probability of the tumour harbouring an <i>NTRK</i> gene fusion. For children with locally advanced or metastatic TRK fusion cancer who have either failed upfront therapy or lack satisfactory treatment options, TRK inhibitor therapy should be considered.https://www.mdpi.com/1718-7729/28/1/38<i>NTRK</i>larotrectinibentrectinibtargeted therapymolecular testingoncogenic drivers |
| spellingShingle | Sébastien Perreault Rose Chami Rebecca J. Deyell Dina El Demellawy Benjamin Ellezam Nada Jabado Daniel A. Morgenstern Aru Narendran Poul H. B. Sorensen Jonathan D. Wasserman Stephen Yip Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Pediatric Patients Current Oncology <i>NTRK</i> larotrectinib entrectinib targeted therapy molecular testing oncogenic drivers |
| title | Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Pediatric Patients |
| title_full | Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Pediatric Patients |
| title_fullStr | Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Pediatric Patients |
| title_full_unstemmed | Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Pediatric Patients |
| title_short | Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Pediatric Patients |
| title_sort | canadian consensus for biomarker testing and treatment of trk fusion cancer in pediatric patients |
| topic | <i>NTRK</i> larotrectinib entrectinib targeted therapy molecular testing oncogenic drivers |
| url | https://www.mdpi.com/1718-7729/28/1/38 |
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