神经营养因子受体酪氨酸激酶（NTRK）的致病性融合事件已在约2％的分化型甲状腺癌（DTC）中描述过。选择性肌动蛋白受体激酶（TRK）抑制剂恩特尼布和拉罗替尼布已在基于1/2期临床试验的肿瘤不可知类型中获得批准。我们在五个转诊中心的真实世界设置中旨在描述NTRK基因融合的患病率以及TRK抑制剂治疗非髓样进展性甲状腺癌（TC）的疗效和安全性。共纳入了进行NTRK基因融合测试的184名TC患者。利用Kaplan-Meier方法估计了接受TRK抑制剂治疗的6例NTRK融合阳性TC患者的无进展生存（PFS）和总生存（OS）概率。其中8/184（4％）患者携带NTRK基因融合。治疗拉永唑替尼四例NTRK1（n = 4）和两例NTRK3（n = 2）基因融合的放射碘（RAI）难治性TC的六名患者。五位患者（83％）已接受至少1次系统治疗，一位患者未接受先前的系统治疗。所有患者在治疗开始前疾病呈形态学进展。客观缓解率为83％，包括两个完全缓解。TRK抑制剂治疗开始后的中位PFS为23个月（95％置信区间[CI]，0-57.4），中位OS没有得出（NR）（95％CI，NR）。不良事件为1-3级。我们RAI难治性TC队列中NTRK基因融合的患病率略高于所有TC患者的报道。在先前接受系统治疗的大多数NTRK基因融合阳性进展性TC患者中，拉永唑替尼是一种有效的治疗选择，并且具有良好的安全性。© 2023. 作者（们）。

Pathogenic fusion events involving neurotrophic receptor tyrosine kinase (NTRK) have been described in ~ 2% of differentiated thyroid cancer (DTC). The selective tropomyosin receptor kinase (TRK) inhibitors entrectinib and larotrectinib have been approved in a tumor agnostic manner based on phase 1/2 clinical trials. In a real-world setting at five referral centers, we aimed to describe the prevalence of NTRK gene fusions and the efficacy and safety of TRK inhibitor treatment for non-medullary, advanced thyroid cancer (TC).A total of 184 TC patients with testing for NTRK gene fusions were included. Progression-free survival (PFS) and overall survival (OS) probabilities were estimated using the Kaplan-Meier method in six patients with NTRK fusion-positive TC who underwent TRK inhibitor therapy.8/184 (4%) patients harbored NTRK gene fusions. Six patients with radioiodine (RAI)-refractory TC harboring NTRK1 (n = 4) and NTRK3 (n = 2) gene fusions were treated with larotrectinib. Five patients (83%) had received ≥ 1 prior systemic therapy and one patient did not receive prior systemic therapy. All patients had morphologically progressive disease before treatment initiation. Objective response rate was 83%, including two complete remissions. Median PFS from start of TRK inhibitor treatment was 23 months (95% confidence interval [CI], 0-57.4) and median OS was not reached (NR) (95% CI, NR). Adverse events were of grade 1-3.The prevalence of NTRK gene fusions in our cohort of RAI-refractory TC is slightly higher than reported for all TC patients. Larotrectinib is an effective treatment option in the majority of NTRK gene fusion-positive advanced TC patients after prior systemic treatment and has a favorable safety profile.© 2023. The Author(s).