Office of Hematology and Oncology Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Clin Cancer Res. 2015 Dec 1;21(23):5205-8. doi: 10.1158/1078-0432.CCR-15-1377. Epub 2015 Aug 31.
The FDA approved lenvatinib (Lenvima, Eisai Inc.) for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory (RAI-refractory) differentiated thyroid cancer (DTC). In an international, multicenter, double-blinded, placebo-controlled trial (E7080-G000-303), 392 patients with locally recurrent or metastatic RAI-refractory DTC and radiographic evidence of disease progression within 12 months prior to randomization were randomly allocated (2:1) to receive either lenvatinib 24 mg orally per day (n = 261) or matching placebo (n = 131) with the option for patients on the placebo arm to receive lenvatinib following independent radiologic confirmation of disease progression. A statistically significant prolongation of progression-free survival (PFS) as determined by independent radiology review was demonstrated [HR, 0.21; 95% confidence interval (CI), 0.16-0.28; P < 0.001, stratified log-rank test], with an estimated median PFS of 18.3 months (95% CI, 15.1, NR) in the lenvatinib arm and 3.6 months (95% CI, 2.2-3.7) in the placebo arm. The most common adverse reactions, in order of decreasing frequency, observed in the lenvatinib-treated patients were hypertension, fatigue, diarrhea, arthralgia/myalgia, decreased appetite, decreased weight, nausea, stomatitis, headache, vomiting, proteinuria, palmar-plantar erythrodysesthesia syndrome, abdominal pain, and dysphonia. Adverse reactions led to dose reductions in 68% of patients receiving lenvatinib at the 24 mg dose and 18% of patients discontinued lenvatinib for adverse reactions leading to residual uncertainty regarding the optimal dose of lenvatinib.
美国食品药品监督管理局（FDA）批准仑伐替尼（Lenvima，卫材公司）用于治疗局部复发或转移性、进行性、放射性碘难治（RAI 难治）的分化型甲状腺癌（DTC）患者。在一项国际性、多中心、双盲、安慰剂对照试验（E7080-G000-303）中，392 名局部复发或转移性 RAI 难治性 DTC 患者和随机分组前 12 个月内有影像学疾病进展证据的患者，按 2:1 的比例随机分配至接受仑伐替尼 24 mg 每日口服治疗（n = 261）或匹配安慰剂（n = 131）治疗，安慰剂组患者在独立影像学确认疾病进展后可选择接受仑伐替尼治疗。独立影像学评估证实，无进展生存期（PFS）得到了统计学显著延长[风险比（HR），0.21；95%置信区间（CI），0.16-0.28；P < 0.001，分层对数秩检验]，仑伐替尼组的中位 PFS 估计为 18.3 个月（95%CI，15.1，NR），安慰剂组为 3.6 个月（95%CI，2.2-3.7）。仑伐替尼治疗患者中，按频率降序排列，最常见的不良反应依次为高血压、疲劳、腹泻、关节痛/肌痛、食欲下降、体重减轻、恶心、口腔炎、头痛、呕吐、蛋白尿、掌跖红细胞感觉不良综合征、腹痛和发音困难。仑伐替尼 24 mg 剂量组 68%的患者和 18%的患者因不良反应而减少剂量，18%的患者因不良反应而停止仑伐替尼治疗，这导致仑伐替尼的最佳剂量仍存在不确定性。
