PDF(Sci-hub)
Abstract：
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.
摘要：
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具有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，在少数罕见肿瘤中以更高的频率(>80%)(例如，唾液腺和乳腺的分泌性癌）。它们通常与其他常见的致癌驱动因素相互排斥。Larotrectinib和entrectinib在TRK融合癌患者的I/II期试验中表现出令人印象深刻的总体缓解率和耐受性，没有其他有效的治疗选择。鉴于TRK融合癌的低频率和加拿大的异质分子检测环境，识别和优化管理这些患者代表了一个新的挑战。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。我们关注五种肿瘤类型：甲状腺癌，大肠癌,非小细胞肺癌,软组织肉瘤,和唾液腺癌.根据肿瘤携带NTRK基因融合的概率，我们还建议在NTRK基因融合检测和治疗方面达成与肿瘤无关的共识.我们建议在没有其他有效治疗选择的所有TRK融合癌患者中考虑使用TRK抑制剂。
