Current Oncology (Jan 2021)

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

  • D. Gwyn Bebb,
  • Shantanu Banerji,
  • Normand Blais,
  • Patrice Desmeules,
  • Sharlene Gill,
  • Andrea Grin,
  • Harriet Feilotter,
  • Aaron R. Hansen,
  • Martin Hyrcza,
  • Monika Krzyzanowska,
  • Barbara Melosky,
  • Jonathan Noujaim,
  • Bibiana Purgina,
  • Dean Ruether,
  • Christine E. Simmons,
  • Denis Soulieres,
  • Emina Emilia Torlakovic,
  • Ming-Sound Tsao

DOI
https://doi.org/10.3390/curroncol28010053
Journal volume & issue
Vol. 28, no. 1
pp. 523 – 548

Abstract

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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 (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.

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