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.

中文翻译：

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加拿大关于成人 TRK 融合癌生物标志物检测和治疗的共识

酪氨酸受体激酶 (TRK) 抑制剂 larotrectinib 和 entrectinib 最近在加拿大被批准用于治疗携带神经营养性酪氨酸受体激酶 (NTRK) 基因融合的实体瘤。这些 NTRK 基因融合是在大多数肿瘤类型中以低频率 (<5%) 发现的致癌驱动因素，在少数罕见肿瘤（例如，唾液腺分泌性癌和乳房）。它们通常与其他常见的致癌驱动因素相互排斥。Larotrectinib 和 entrectinib 在无其他有效治疗选择的 TRK 融合癌患者的 I/II 期试验中显示出令人印象深刻的总体反应率和耐受性。鉴于 TRK 融合癌症的低频率和加拿大的异质分子检测环境，识别和优化管理此类患者是一项新的挑战。我们就何时以及如何测试 NTRK 基因融合以及何时考虑使用 TRK 抑制剂进行治疗提供了加拿大共识。我们专注于五种肿瘤类型：甲状腺癌、结直肠癌、非小细胞肺癌、软组织肉瘤和唾液腺癌。基于肿瘤携带 NTRK 基因融合的可能性，我们还建议对 NTRK 基因融合检测和治疗达成与肿瘤无关的共识。我们建议在所有没有其他有效治疗选择的 TRK 融合癌患者中考虑使用 TRK 抑制剂。甲状腺癌、结直肠癌、非小细胞肺癌、软组织肉瘤和唾液腺癌。基于肿瘤携带 NTRK 基因融合的可能性，我们还建议对 NTRK 基因融合检测和治疗达成与肿瘤无关的共识。我们建议在所有没有其他有效治疗选择的 TRK 融合癌患者中考虑使用 TRK 抑制剂。甲状腺癌、结直肠癌、非小细胞肺癌、软组织肉瘤和唾液腺癌。基于肿瘤携带 NTRK 基因融合的可能性，我们还建议对 NTRK 基因融合检测和治疗达成与肿瘤无关的共识。我们建议在所有没有其他有效治疗选择的 TRK 融合癌患者中考虑使用 TRK 抑制剂。