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仑伐替尼在实体瘤治疗中的应用。

Lenvatinib in Management of Solid Tumors.

机构信息

Department of Medicine, Division of Medical Oncology, University of Kentucky College of Medicine, Lexington, Kentucky, USA.

Markey Cancer Center, Lexington, Kentucky, USA.

出版信息

Oncologist. 2020 Feb;25(2):e302-e310. doi: 10.1634/theoncologist.2019-0407. Epub 2019 Oct 14.

DOI:10.1634/theoncologist.2019-0407
PMID:32043789
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7011622/
Abstract

Lenvatinib is a type I tyrosine kinase inhibitor exhibiting powerful antiangiogenic activity in cancer therapy. Displaying activity in multiple solid tumors, it has been approved in differentiated thyroid cancer, hepatocellular carcinoma, and renal cell carcinoma as single agent or in combination. In addition, lenvatinib has shown promise in several other tumor types including medullary, anaplastic thyroid, adenoid cystic, and endometrial cancer. Exploring synergy between angiogenic and immune checkpoint inhibitors, the lenvatinib/pembrolizumab combination is poised to become the next pair of active drugs in endometrial, lung, and gastrointestinal malignancies. Despite robust activity, the drug can be difficult to tolerate. Optimization of dose and biomarkers for prediction of efficacy and toxicities will be of great help. IMPLICATIONS FOR PRACTICE: Readers will be presented with an update on U.S. Food and Drug Administration approval of lenvatinib and suggestions for off-label use in thyroid cancer and adenoid cystic carcinomas. They will become familiarized with the common side effects, frequency, and predicators of response. In addition, they will learn that different strengths of lenvatinib are prescribed and why. Finally, readers are pointed to the latest efforts to combine lenvatinib and pembrolizumab, as well as to unresolved issues such as long-term side effects/toxicities of this drug.

摘要

乐伐替尼是一种 I 型酪氨酸激酶抑制剂,在癌症治疗中具有强大的抗血管生成活性。在多种实体肿瘤中显示出活性,已被批准作为单一药物或联合用药用于分化型甲状腺癌、肝细胞癌和肾细胞癌。此外,乐伐替尼在其他几种肿瘤类型中也显示出希望,包括髓样甲状腺癌、间变性甲状腺癌、腺样囊性癌和子宫内膜癌。探索血管生成和免疫检查点抑制剂的协同作用,乐伐替尼/帕博利珠单抗联合用药有望成为子宫内膜癌、肺癌和胃肠道恶性肿瘤的下一对有效药物。尽管具有强大的活性,但该药物可能难以耐受。优化剂量和预测疗效和毒性的生物标志物将有很大帮助。

临床意义

读者将了解到乐伐替尼获得美国食品和药物管理局批准的最新情况,并了解到其在甲状腺癌和腺样囊性癌中的非适应证应用建议。他们将熟悉常见的副作用、频率和反应预测因素。此外,他们将了解到乐伐替尼的不同剂量强度以及为什么会有不同的剂量强度。最后,读者将了解到乐伐替尼与帕博利珠单抗联合应用的最新进展,以及该药物的长期副作用/毒性等尚未解决的问题。

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Phase II Study of Lenvatinib in Patients With Progressive, Recurrent or Metastatic Adenoid Cystic Carcinoma.仑伐替尼治疗进展性、复发性或转移性腺样囊性癌患者的 II 期研究。
J Clin Oncol. 2019 Jun 20;37(18):1529-1537. doi: 10.1200/JCO.18.01859. Epub 2019 Apr 2.
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Distribution and Activity of Lenvatinib in Brain Tumor Models of Human Anaplastic Thyroid Cancer Cells in Severe Combined Immune Deficient Mice.在严重联合免疫缺陷小鼠的人未分化甲状腺癌细胞脑肿瘤模型中仑伐替尼的分布和活性。
Mol Cancer Ther. 2019 May;18(5):947-956. doi: 10.1158/1535-7163.MCT-18-0695. Epub 2019 Mar 29.
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Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer (IMpower150): key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial.阿替利珠单抗联合贝伐珠单抗和化疗治疗非小细胞肺癌(IMpower150):一项随机、开放标签的 3 期临床试验中具有 EGFR 突变或基线肝转移患者的关键亚组分析。
Lancet Respir Med. 2019 May;7(5):387-401. doi: 10.1016/S2213-2600(19)30084-0. Epub 2019 Mar 25.
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Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial.仑伐替尼联合帕博利珠单抗治疗晚期子宫内膜癌患者:一项多中心、开放标签、单臂、2 期临床试验的中期分析。
Lancet Oncol. 2019 May;20(5):711-718. doi: 10.1016/S1470-2045(19)30020-8. Epub 2019 Mar 25.
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Efficacy and tolerability of initial low-dose lenvatinib to treat differentiated thyroid cancer.初始低剂量乐伐替尼治疗分化型甲状腺癌的疗效和耐受性。
Medicine (Baltimore). 2019 Mar;98(10):e14774. doi: 10.1097/MD.0000000000014774.
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