Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Adults†
Tom Baker Cancer Centre and University of Calgary, Calgary, AB T2N 4N2, Canada
Research Institute in Oncology and Hematology, CancerCare Manitoba, University of Manitoba, Winnipeg, MB R3E 0V9, Canada
Centre Hospitalier Universitaire de Montreal, Department of Medicine, University of Montreal, Montreal, QC H2X 3E4, Canada
Service D’Anatomopathologie et de Cytologie, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, QC G1V 0A6, Canada
BC Cancer, Vancouver, BC V5Z 4E6, Canada
Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON K7L 3N6, Canada
Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canada
Department of Pathology and Laboratory Medicine, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB T2N 4Z6, Canada
Hôpital Maisonneuve-Rosemont, Montreal, QC H1T 2M4, Canada
The Ottawa Hospital, Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, ON K1N 6N5, Canada
Department of Oncology, Tom Baker Cancer Centre, Calgary, AB T2N 4N2, Canada
Department of Pathology and Laboratory Medicine, Saskatchewan Health Authority and University of Saskatchewan, Saskatoon, SK S7N 5B5, Canada
Department of Pathology, Laboratory Medicine Program, University Health Network, Toronto, ON M5G 2C4, Canada
Authors to whom correspondence should be addressed.
Another group of Canadian authors (Perreault et al.) has developed a consensus for testing and treatment algorithms for TRK fusion cancer in pediatric patients, published in this issue of Current Oncology (Curr. Oncol. 2021, 28(1), 346–366).
Curr. Oncol. 2021, 28(1), 523-548; https://doi.org/10.3390/curroncol28010053
Received: 2 December 2020 / Revised: 31 December 2020 / Accepted: 8 January 2021 / Published: 15 January 2021
The tyrosine receptor kinase (TRK) inhibitors larotrectinib and entrectinib were recently approved in Canada for the treatment of solid tumours harbouring neurotrophic tyrosine receptor kinase (NTRK) gene fusions. These NTRK gene fusions are oncogenic drivers found in most tumour types at a low frequency (<5%), and at a higher frequency (>80%) in a small number of rare tumours (e.g., secretory carcinoma of the salivary gland and of the breast). They are generally mutually exclusive of other common oncogenic drivers. Larotrectinib and entrectinib have demonstrated impressive overall response rates and tolerability in Phase I/II trials in patients with TRK fusion cancer with no other effective treatment options. Given the low frequency of TRK fusion cancer and the heterogeneous molecular testing landscape in Canada, identifying and optimally managing such patients represents a new challenge. We provide a Canadian consensus on when and how to test for NTRK gene fusions and when to consider treatment with a TRK inhibitor. We focus on five tumour types: thyroid carcinoma, colorectal carcinoma, non-small cell lung carcinoma, soft tissue sarcoma, and salivary gland carcinoma. Based on the probability of the tumour harbouring an NTRK gene fusion, we also suggest a tumour-agnostic consensus for NTRK gene fusion testing and treatment. We recommend considering a TRK inhibitor in all patients with TRK fusion cancer with no other effective treatment options.