Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Adults

• Published in: Current oncology (Toronto) Vol. 28; no. 1; pp. 523 - 548
• Main Authors: Bebb, D Gwyn, Banerji, Shantanu, Blais, Normand, Desmeules, Patrice, Gill, Sharlene, Grin, Andrea, Feilotter, Harriet, Hansen, Aaron R, Hyrcza, Martin, Krzyzanowska, Monika, Melosky, Barbara, Noujaim, Jonathan, Purgina, Bibiana, Ruether, Dean, Simmons, Christine E, Soulieres, Denis, Torlakovic, Emina Emilia, Tsao, Ming-Sound
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 15-01-2021; MDPI AG
• Subjects: entrectinib; Guidelines; larotrectinib; molecular testing; NTRK; oncogenic drivers; targeted therapy; targeted therapy; larotrectinib; oncogenic drivers; molecular testing; entrectinib; tumour-agnostic; NTRK; TRK fusion
• ISSN: 1718-7729; 1198-0052; 1718-7729
• DOI: 10.3390/curroncol28010053

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 (
gene fusions. These
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
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
gene fusion, we also suggest a tumour-agnostic consensus for
gene fusion testing and treatment. We recommend considering a TRK inhibitor in all patients with TRK fusion cancer with no other effective treatment options.