[A Case of Pediatric Soft Tissue Sarcoma with LMNA-NTRK1 Gene Fusion Treated with Larotrectinib under Single Patient Expanded Access System].
[A Case of Pediatric Soft Tissue Sarcoma with LMNA-NTRK1 Gene Fusion Treated with Larotrectinib under Single Patient Expanded Access System].
复制标题
单患者扩大准入系统下拉罗替尼治疗LMNA-NTRK1基因融合的小儿软组织肉瘤一例
DOI：
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Y. Suehara
中科院分区：
文献类型：
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作者：
S. Kato;J. Fujimura;Y. Nozaki;Shigeo Yamaguchi;T. Takagi;T. Hayashi;Tsuyoshi Saito;Dahlia N. Henry;N. Ku;Y. Suehara
原肌球蛋白相关激酶(TRK)融合蛋白是成人和儿童多种肿瘤的致癌因素。美国批准的口服选择性TRK抑制剂Larotrectinib对含有TRK融合的肿瘤显示出抑制活性，且耐受性良好。我们报告一例8岁女孩使用larotrectinib治疗的NTRK融合低级别肉瘤复发。该患者曾在6岁时切除右臂低级别肉瘤，但16个月后局部复发。拉洛替尼开始剂量为100 mg BID。3个月后放射学完全缓解。没有因拉洛替尼治疗而引起的不良反应。给药6个月后，我们进行了局部切除，确认病理完全缓解。切除后4个月停止用药，患者没有复发的证据。在这种情况下，拉洛替尼是通过FDA下的单个患者扩大通路获得的。在本文中，我们还讨论了在日本精确医学时代，获取未经批准的药物所面临的问题。
Tropomyosin-related kinase(TRK)fusion proteins are oncogenic drivers in multiple tumors in adults and children.Larotrectinib, an orally administered selective TRK inhibitor approved in the US, exhibits inhibitory activity against tumors harboring TRK fusions and is well tolerated.Here, we report the case of an 8-year-old female child with recurrence of an NTRK fusion low-grade sarcoma treated with larotrectinib monotherapy.The patient previously underwent resection of low-grade sarcoma in the right brachialis at 6 years of age, but local recurrence occurred after 16 months.As re-operation likely required amputation, larotrectinib was commenced at a dose of 100 mg BID.Complete radiographic remission was achieved after 3 months.There were no adverse events attributed to larotrectinib treatment.After dosing for 6 months, we performed local resection, confirming pathological complete remission.The drug was stopped, and the patient showed no evidence of relapse at 4 months after resection.In this case, larotrectinib was obtained using Single Patient Expanded Access under the FDA.In this paper, we also discuss the issues faced while accessing unapproved drugs in the precision medicine era in Japan.