——新型口服抗癌药Lenvima（lenvatinib）-将成为甲状腺癌治疗的新方法 2月13日，美国FDA批准Lenvima (lenvatinib)治疗侵袭性、分化型甲状腺癌(DTC)患者，适用于在接受放射性碘治疗后疾病仍恶化（放射性碘难治性疾病）的患者。 DTC是最常见形式的甲状腺癌，它是甲状腺的一种癌性增长，甲状腺位于颈部，它有助于调节人体的代谢。国家癌症研究所预计2014年有6.298万人确诊患有甲状腺癌，有1890人死于这种疾病。Lenvima是一种激酶抑制剂，它通过阻断某些蛋白帮助癌细胞生长及分化起作用。 “帮助难治性疾病患者的新治疗药物的开发是FDA高度重视的事情，”FDA药物评价与研究中心代谢与肿瘤产品办公室主任、医学博士Pazdur称。“今天的批准为患者及卫生保健专业人员提供了一种新的治疗药物，可以帮助延缓DTC的恶化。” Lenvima是在FDA优先审评程序下完成审评的，优先审评为药物的审评提供了一个加快的审评，如果药物获得批准，它将对严重疾病的治疗在安全性及有效性上提供明显的改善。 批准日期： 2015年2月13日；公司：卫才Eisai Co.，Ltd. 注：以下产品不同的国家上市，不同的价格，采购以咨询为准 美国包装 LENVIMA  capsules 10MG 30  lenvatinib mesylate   NDC 62856-710-30 LENVIMA  capsules 14MG 30  lenvatinib mesylate   NDC 62856-714-30    LENVIMA  capsules 20MG 30  lenvatinib mesylate   NDC 62856-720-30 LENVIMA  capsules 24MG 30  lenvatinib mesylate   NDC 62856-724-30 德国包装 LENVIMA  capsules 4MG 30 LENVIMA  capsules 10MG 30 日本包装 LENVIMA  capsules 4MG 30 LENVIMA  capsules 4MG 30 韩国包装 LENVIMA  capsules 4MG 30 LENVIMA  capsules 4MG 30 Lenvima™ (lenvatinib mesylate) is a multiple receptor tyrosine kinase (RTK) inhibitor indicated for the treatment of thyroid cancer. LENVIMA® (lenvatinib) capsules  LENVIMA- lenvatinib    Eisai Inc. LENVIMA Rx Pharmacological Class: Kinase inhibitor. Active Ingredient(s): Lenvatinib 4mg, 10mg; capsules. Company Eisai Pharmaceuticals Indication(s): Treatment of locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer. Pharmacology: Lenvatinib is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Also, lenvatinib inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions. Clinical Trials: A multi-center, randomized, double-blind, placebo-controlled trial was conducted in 392 patients with locally recurrent or metastatic radioactive iodine-refractory differentiated thyroid cancer and radiographic evidence of disease progression within 12 months prior to randomization. Patients were randomized (2:1) to receive Lenvima 24mg once daily (n=261) or placebo (n=131) until disease progression. The major efficacy outcome measure was progression-free survival (PFS) as determined by blinded independent radiologic review using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. A statistically significant prolongation in PFS was demonstrated in Lenvima-treated patients vs. those receiving placebo (18.3 months vs. 3.6 months; HR 0.21 [95% CI: 0.16, 0.28]; P<0.001). A higher objective response rate was seen in Lenvima-treated patients vs. those receiving placebo (65% vs. 2%; P<0.001). A partial response was higher in the Lenvima-treated group vs. the placebo group (63% vs. 2%). For more clinical trial data, see full labeling. Legal Classification: Rx Adults: 24mg once daily until disease progression or unacceptable toxicity occurs. Severe renal impairment (CrCl <30mL/min) or severe hepatic impairment (Child-Pugh C): 14mg once daily. Dose modifications for adverse reactions or lab abnormalities: see full labeling. Children: Not established. Warnings/Precautions: Control blood pressure prior to treatment; monitor after 1 week, every 2 weeks for the first 2 months, and then at least monthly thereafter during therapy. Discontinue if life-threatening hypertension, Grade 4 cardiac dysfunction or hemorrhage, arterial thrombotic event, hepatic failure, nephrotic syndrome, GI perforation or life-threatening fistula, or severe and persistent neurologic symptoms occur. Withhold if Grade 3 hypertension persists despite therapy, Grade 3 cardiac dysfunction or hemorrhage, ≥Grade 3 liver impairment or QT prolongation, Grade 3 or 4 renal failure/impairment, ≥2g of proteinuria/24hrs, or reversible posterior leukoencephalopathy syndrome (RPLS) occurs. Monitor for signs/symptoms of cardiac decompensation. Monitor liver function prior to treatment, every 2 weeks for the first 2 months, then at least monthly during treatment. Monitor for proteinuria prior to, and periodically during treatment. Dehydration. Hypovolemia. Congenital long QT syndrome, CHF, bradyarrhythmias, or those taking Class Ia or III antiarrhythmic drugs; monitor ECGs. Monitor and correct electrolyte abnormalities. Monitor blood calcium levels at least monthly; replace as needed during treatment. Monitor thyroid stimulating hormone levels monthly; adjust replacement therapy as needed. Pregnancy: avoid. Use effective contraception during treatment and for at least 2 weeks after treatment completion. Lactation: discontinue nursing. Adverse Reaction(s) Hypertension, fatigue, diarrhea, arthralgia/myalgia, decreased appetite, weight decreased, nausea, stomatitis, headache, vomiting, proteinuria, palmar-plantar erythrodysesthesia syndrome, abdominal pain, dysphonia. How Supplied: Blister cards—6 LAST UPDATED: 4/10/2015 Indication: LENVIMA® (lenvatinib) is indicated for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC). Important Safety Information Warnings and Precautions •Hypertension reported in 73% of patients on LENVIMA vs 16% for placebo (44% vs 4% ≥grade 3). Blood pressure should be controlled prior to treatment. Withhold dose for grade 3 hypertension despite optimal antihypertensive therapy; resume at reduced dose when controlled at ≤grade 2. Discontinue for life-threatening hypertension •Cardiac dysfunction reported in 7% of patients on LENVIMA vs 2% for placebo (2% vs 0% ≥grade 3). Monitor for signs/symptoms of cardiac decompensation. Withhold for grade 3 cardiac dysfunction. Resume at reduced dose or discontinue based on severity and persistence of cardiac dysfunction. Discontinue for grade 4 cardiac dysfunction •Arterial thromboembolic events reported in 5% of patients on LENVIMA vs 2% for placebo (3% vs 1% ≥grade 3). Discontinue following an arterial thrombotic event. The safety of resuming LENVIMA after an arterial thromboembolic event has not been established, and LENVIMA has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months •ALT and AST increases (≥grade 3) occurred in 4% and 5% of patients on LENVIMA vs 0% for placebo. Across clinical studies in which 1108 patients received LENVIMA, hepatic failure (including fatal events) was reported in 3 patients and acute hepatitis in 1 patient. Monitor liver function before initiation, then every 2 weeks for first 2 months, and at least monthly thereafter during treatment. Withhold dose for liver impairment ≥grade 3. Resume at reduced dose or discontinue based on severity/persistence of hepatotoxicity. Discontinue for hepatic failure •Proteinuria reported in 34% of patients on LENVIMA vs 3% for placebo (11% vs 0% ≥grade 3). Monitor for proteinuria before and during treatment. Withhold dose for ≥2 grams of proteinuria/24 hours. Resume at reduced dose when proteinuria is <2 gm/24 hours. Discontinue for nephrotic syndrome •Events of renal impairment reported in 14% of patients on LENVIMA vs 2% for placebo (3% vs 1% ≥grade 3). Withhold LENVIMA for grade 3 or 4 renal failure/impairment. Resume at reduced dose or discontinue, depending on severity/persistence of renal impairment •Events of gastrointestinal (GI) perforation or fistula reported in 2% of patients on LENVIMA vs 0.8% for placebo. Discontinue in patients who develop GI perforation or life-threatening fistula •QT/QTc interval prolongation reported in 9% of patients on LENVIMA vs 2% for placebo (2% vs 0% ≥grade 3). Monitor ECG in patients with congenital long QT syndrome, CHF, bradyarrhythmias, or patients taking drugs known to prolong the QT interval. Monitor and correct electrolyte abnormalities in all patients. Withhold dose for ≥grade 3 QT interval prolongation. Resume at reduced dose when QT prolongation resolves to grade 0, 1, or baseline •Hypocalcemia ≥grade 3 reported in 9% of patients on LENVIMA (2% for placebo). Monitor blood calcium levels at least monthly and replace calcium as necessary. Interrupt and adjust LENVIMA as necessary. In most cases, hypocalcemia responded to replacement and dose interruption/reduction •Across clinical studies in which 1108 patients received LENVIMA, reversible posterior leukoencephalopathy syndrome (RPLS) was reported in 3 patients. Withhold LENVIMA for RPLS until fully resolved. Resume at reduced dose or discontinue based on the severity and persistence of neurologic symptoms •Hemorrhagic events occurred in 35% of patients on LENVIMA vs 18% for placebo (2% vs 3% ≥grade 3). The most frequently reported hemorrhagic event was epistaxis (11% grade 1 and 1% grade 2). Discontinuation due to hemorrhagic events occurred in 1% of patients on LENVIMA. There was 1 fatal intracranial hemorrhage case among 16 patients who received LENVIMA and had CNS metastases at baseline. Withhold dose for grade 3 hemorrhage. Resume at reduced dose or discontinue, based on severity/persistence of hemorrhage. Discontinue for grade 4 hemorrhage •LENVIMA impairs exogenous thyroid suppression. In patients with a normal baseline TSH, elevation of TSH level above 0.5 mU/L was observed post baseline in 57% of patients on LENVIMA (14% for placebo). Monitor TSH levels monthly and adjust thyroid replacement medication as needed in patients with DTC •LENVIMA may cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with LENVIMA and for at least 2 weeks following completion of therapy Adverse Reactions •The most common adverse reactions observed in LENVIMA-treated patients vs placebo-treated patients were hypertension (73% vs 16%), fatigue (67% vs 35%), diarrhea (67% vs 17%), arthralgia/myalgia (62% vs 28%), decreased appetite (54% vs 18%), weight decreased (51% vs 15%), nausea (47% vs 25%), stomatitis (41% vs 8%), headache (38% vs 11%), vomiting (36% vs 15%), proteinuria (34% vs 3%), palmar-plantar erythrodysesthesia syndrome (32% vs 1%), abdominal pain (31% vs 11%), and dysphonia (31% vs 5%) Use in Specific Populations •Because of the potential for serious adverse reactions in nursing infants, advise women to discontinue breastfeeding during treatment •LENVIMA may result in reduced fertility in females of reproductive potential, and may result in damage to male reproductive tissues, leading to reduced fertility of unknown duration Please see full Prescribing Information. RAI=radioactive iodine; DTC=differentiated thyroid cancer; VEGF=vascular endothelial growth factor; VEGFR=vascular endothelial growth factor receptor; RECIST=Response Evaluation Criteria in Solid Tumors; ORR=objective response rate; OS=overall survival. LENVIMA was studied in SELECT (Study of [E7080] LEnvatinib in Differentiated Cancer of the Thyroid), a multicenter, randomized (2:1), double-blind, placebo-controlled trial conducted in 392 patients with locally recurrent or metastatic RAI-refractory DTC and radiographic evidence of disease progression within 12 months prior to randomization, confirmed by independent radiologic review. RAI-refractory was defined as 1 or more measurable lesions with no iodine uptake on RAI scan, iodine uptake with progression within 12 months of RAI therapy, or having received cumulative RAI activity of >600 mCi (22 GBq) with the last dose administered at least 6 months prior to study entry. Patients were randomized to receive LENVIMA 24 mg once daily (n=261) or placebo (n=131) until disease progression. Randomization was stratified by geographic region, prior VEGF/VEGFR-targeted therapy, and age. The primary end point was PFS, as determined by blinded, independent, radiologic review using RECIST 1.1. Independent review confirmation of disease progression was required prior to discontinuing patients from the randomization phase of the study. Secondary end points included ORR and OS. Patients in the placebo arm could receive LENVIMA following independent review confirmation of disease progression.1 https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=f4bedd21-efde-44c6-9d9c-b48b78d7ed1e