Department of Medicine, Division of Medical Oncology, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
Markey Cancer Center, Lexington, Kentucky, USA.
Oncologist. 2020 Feb;25(2):e302-e310. doi: 10.1634/theoncologist.2019-0407. Epub 2019 Oct 14.
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.
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。
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。