Elghawy Omar, Barsouk Adam, Heidlauf Alec, Chen Simon, Cohen Roger B, Sun Lova
Division of Hematology/Oncology, Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA.
J Endocr Soc. 2024 Sep 9;8(10):bvae158. doi: 10.1210/jendso/bvae158. eCollection 2024 Aug 27.
The real world efficacy and tolerabiltiy of NTRK inhibitor larotrectinib has not yet been reported in the literature although trial data has shown promising results.
We report a retrospective analysis of patients with thyroid cancer harboring fusions who underwent treatment with larotrectinib.
A single-institution, retrospective case series of patients with fusion-positive thyroid cancers treated with neurotrophic tyrosine receptor kinase ( inhibitors from January 1, 2007, to January 1, 2023, was performed. This study was conducted at a single academic tertiary referral center. Patients with confirmed -fusion thyroid cancer who received larotrectinib were included. Larotrectinib was administered in accordance with clinical judgment from oncology providers. The primary end point was progression-free survival (PFS).
Eight patients with fusion-positive thyroid cancer treated with larotrectinib were identified: 4 with papillary thyroid cancer (PTC) (50%), 3 with poorly differentiated thyroid cancer (PDTC) (38%), and 1 with anaplastic thyroid cancer (ATC) (12%). The median PFS (mPFS) for all patients was 24.7 months (95% CI, 11.3-38.1). mPFS in PTC was higher than PDTC (34.6 months [24.7-48.7 months] vs 17.5 [7.1-21.1 months]; = .017). The median overall survival (OS) was 43.8 months (29.8-56.8 months) overall. The single patient with ATC had a PFS and OS of 23 months. Two patients remained on treatment/alive at data cutoff, with a duration of response of 33.5 months and a median follow-up of 52 months. Patients achieved 1 complete response (12%), 6 partial responses (75%), and 1 stable disease (12%).
In this single-institution cohort of patients with fusion-positive thyroid cancer, inhibition led to an mPFS of 25 months, with survival surpassing historic benchmarks for ATC and PDTC.
尽管试验数据显示出有前景的结果，但神经营养性酪氨酸受体激酶（NTRK）抑制剂拉罗替尼在现实世界中的疗效和耐受性尚未见文献报道。
我们报告了对接受拉罗替尼治疗的携带融合基因的甲状腺癌患者的回顾性分析。
对2007年1月1日至2023年1月1日在单一学术三级转诊中心接受神经营养性酪氨酸受体激酶（NTRK）抑制剂治疗的融合基因阳性甲状腺癌患者进行单机构回顾性病例系列研究。纳入确诊为融合基因阳性甲状腺癌且接受拉罗替尼治疗的患者。拉罗替尼根据肿瘤学专家的临床判断给药。主要终点为无进展生存期（PFS）。
确定了8例接受拉罗替尼治疗的融合基因阳性甲状腺癌患者：4例为乳头状甲状腺癌（PTC）（50%），3例为低分化甲状腺癌（PDTC）（38%），1例为间变性甲状腺癌（ATC）（12%）。所有患者的中位无进展生存期（mPFS）为24.7个月（95%CI，11.3 - 38.1）。PTC患者的mPFS高于PDTC（34.6个月[24.7 - 48.7个月]对17.5个月[7.1 - 21.1个月]；P = 0.017）。总体中位总生存期（OS）为43.8个月（29.8 - 56.8个月）。唯一的ATC患者的PFS和OS为23个月。在数据截止时，2例患者仍在接受治疗/存活，缓解持续时间为33.5个月，中位随访时间为52个月。患者达到1例完全缓解（12%），6例部分缓解（75%），1例病情稳定（12%）。
在这个单机构的融合基因阳性甲状腺癌患者队列中，NTRK抑制导致mPFS为25个月，生存期超过了ATC和PDTC的历史基准。
