The identification of oncogenic fusions and the development of selective tyrosine kinase inhibitors have revolutionised the therapeutic approach for several solid tumours. Neurotrophic tropomyosin receptor kinase (NTRK) rearrangements have been described in most solid tumours, with variable frequencies, ranging from less than 1% in high-prevalence tumours (eg, non-small-cell lung cancer [NSCLC] and breast cancer), to 5–25% in some tumour types (eg, papillary thyroid cancer and Spitzoid neoplasms), to more than 90% in uncommon histotypes (eg, secretory breast carcinoma and mammary analogue secretory carcinoma). Multiple TRK inhibitors with different properties are available or under clinical development ( ). Larotrectinib was the first-in-class TRK inhibitor approved for metastatic, inoperable NTRK fusion-positive solid tumours and the second tumour-agnostic US Food and Drug Administration (FDA)-approved drug, based on the impressive results of three open-label, single-group, phase 1/2 studies. The preliminary analysis of the first 55 patients enrolled in the phase 1 studies showed a 75% overall response by independent review committee, with median duration of response and median progression-free survival not reached. Larotrectinib was also well tolerated, with most adverse events being of grade 1–2 severity, and no treatment-related adverse events of grade 3–4 in 5% or more of the patients.

中文翻译：

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NTRK基因融合体：准备闪耀的毛坯钻石。

致癌融合的鉴定和选择性酪氨酸激酶抑制剂的开发彻底改变了几种实体瘤的治疗方法。已经在大多数实体瘤中描述了神经营养性原肌球蛋白受体激酶（NTRK）的重排，其频率范围不等，从高发性肿瘤（例如非小细胞肺癌[NSCLC]和乳腺癌）到小于1％在某些肿瘤类型（例如，甲状腺乳头状癌和类鼻咽癌）中占5–25％，在罕见的组织类型中（例如，分泌性乳腺癌和类似乳腺分泌性癌）超过90％。多种具有不同特性的TRK抑制剂已经上市或正在临床开发中。Larotrectinib是首个被批准用于转移性，不可手术的NTRK的TRK抑制剂融合阳性实体瘤和美国食品药品监督管理局（FDA）批准的第二种与肿瘤无关的药物，基于三项开放标签，单组，1/2期研究的令人印象深刻的结果。对参与1期研究的前55名患者的初步分析显示，独立审查委员会的总体缓解率为75％，未达到中位缓解持续时间和中位无进展生存期。拉罗替尼的耐受性也很好，在5％或以上的患者中，大多数不良反应为1–2级严重度，没有与治疗相关的3–4级不良事件。