近日，美国食品药品监督管理局(FDA)批准KADCYLA(ADO-TRASTUZUMAB EMTANSINE)VIAL SINGLE-USE，为有HER2-阳性，晚期(转移)乳癌患者一种新治疗。 HER2是一种涉及正常细胞生长蛋白。发现在某些类型癌症细胞(HER2-阳性)量增加，包括某些乳癌。在这些HER2-阳性乳癌中，HER2蛋白量增加影响癌细胞生长和生存。 Kadcyla意向为既往用曲妥珠单抗[trastuzumab]，另一种抗-HER2治疗，和紫衫烷，一类常用于治疗乳癌的化疗药治疗过的患者。 FDA的药物评价和研究中心血液学和肿瘤室主任Richard Pazdur，M.D.说：“Kadcyla是曲妥珠单抗与一个干扰癌细胞生长被称为DM1药连接，”“Kadcyla输送药物至癌部位缩小肿瘤，减慢疾病进展和延长生存。是第四个靶向HER2蛋白被批准药物。” 批准日期：2013年2月22日；公司：Genentech，Inc. KADCYLA（曲妥珠单抗[ado-trastuzumab emtansine]）用于注射，用于静脉内使用 美国首次批准：2013年 警告： 致死性，心脏毒性，胚胎毒性查看完整的盒装警告的完整处方信息 不要用KADCYLA替代或用曲妥珠单抗替代。 在KADCYLA治疗的患者中发生了肝毒性，肝衰竭和死亡。在开始之前和每次剂量之前监测肝功能。研究所剂量修改或永久中断适当。 KADCYLA可能导致左心室射血分数（LVEF）的降低。在开始之前评估LVEF。监测和保留给药或中止适当。 胚胎-胎儿毒性：怀孕期间暴露于KADCYLA可导致胚胎-胎儿伤害。建议患者这些风险和有效避孕的需要。 近期主要变化 盒装警告：04/2016 剂量和管理：05/2015 警告和注意事项：05/2015 作用机制 Ado-trastuzumab emtansine是HER2靶向的抗体-药物偶联物。 抗体是人源化抗HER2 IgG1，曲妥珠单抗。 小分子细胞毒素DM1是微管抑制剂。在结合HER2受体的亚结构域IV后，曲妥珠单抗美登素经历受体介导的内化和随后的溶酶体降解，导致含有DM1的细胞毒性分解代谢物的细胞内释放。DM1与微管蛋白的结合破坏细胞中的微管网络，其导致细胞周期停滞和凋亡性细胞死亡。 此外，体外研究表明，类似于曲妥珠单抗，阿曲古妥珠单抗美登素抑制HER2受体信号传导，介导抗体依赖性细胞介导的细胞毒性，并抑制过度表达HER2的人乳腺癌细胞中HER2细胞外结构域的脱落 适应症和用法 KADCYLA是HER2靶向抗体和微管抑制剂缀合物，作为单一药剂，用于治疗HER2阳性的转移性乳腺癌患者，所述HER2阳性，转移性乳腺癌先前分别或组合接受曲妥珠单抗和紫杉烷。患者应该有： 接受先前治疗转移性疾病，或 在完成辅助治疗的6个月内或在6个月内发展的疾病复发。 剂量和给药 仅用于静脉输注。不要作为静脉推注或推注给药。不要使用葡萄糖（5％）溶液。 KADCYLA的推荐剂量为3.6mg/kg，作为每3周（21天周期）的静脉内输注，直到疾病进展或不可接受的毒性。不要以大于3.6mg/kg的剂量施用KADCYLA。不要用KADCYLA替代或用曲妥珠单抗替代。 不良事件（输注相关反应，肝毒性，左心室心脏功能障碍，血小板减少，肺部毒性或周围神经病变）的管理可能需要暂时中断，减少剂量或停止治疗KADCYLA。 剂量形式和强度 冻干粉末在一次性小瓶中，每瓶含有100毫克或每瓶160毫克。 禁忌症 没有。 警告和注意事项 肺毒性：在诊断为间质性肺病或肺炎的患者中永久停用KADCYLA。 输液相关反应，超敏反应：监测输液期间和之后的体征和症状。如果发生显着的输注相关反应或超敏反应，则减慢或中断输注并施用适当的医学治疗。永久停止KADCYLA的危及生命的输液相关反应。 出血：在没有已知确定的危险因素的患者中，以及在血小板减少症患者和接受抗凝血和抗血小板治疗的患者中，在临床试验中发生致死性出血。使用这些试剂时要小心，并在医疗上同时使用时考虑额外的监测。 血小板减少：在每次KADCYLA剂量之前监测血小板计数。适当调整剂量修改。 神经毒性：监测体征或症状。对于经历3或4级外周神经病变的患者暂时停止给药。 HER2测试：使用经过FDA批准的实验室进行的测试，证明其熟练。 不良反应 与KADCYLA（n=884名治疗的患者）最常见的不良药物反应（频率> 25％）是疲劳，恶心，肌肉骨骼疼痛，出血，血小板减少，头痛，转氨酶增加，便秘和鼻出血。 在特定人群中使用 哺乳：建议不要哺乳。 女性和男性的生殖潜力：验证女性在KADCYLA开始之前的怀孕状态。 完整资料附件： https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=23f3c1f4-0fc8-4804-a9e3-04cf25dd302e KADCYLA(ADO-TRASTUZUMAB EMTANSINE)VIAL SINGLE-USE KADCYLA(ado-trastuzumab emtansine), as a single agent, is indicated for the treatment of patients with HER2-positive (HER2+), metastatic breast cancer (MBC) who previously received trastuzumab and a taxane, separately or in combination. Patients should have either: Received prior therapy for metastatic disease, or Developed disease recurrence during or within six months of completing adjuvant therapy KADCYLA (ado-trastuzumab emtansine) playpauseHear it pronouncedImportant Safety Information Warnings and Precautions Hepatotoxicity (Boxed WARNING) Hepatotoxicity, predominantly in the form of asymptomatic increases in the concentrations of serum transaminases, has been observed in clinical trials with KADCYLA. Serious hepatobiliary disorders, including at least 2 fatal cases of severe drug-induced liver injury and associated hepatic encephalopathy, have been reported in clinical trials with KADCYLA. Some of the observed cases may have been confounded by comorbidities and concomitant medications with known hepatotoxic potential. Monitor serum transaminases and bilirubin prior to initiation of KADCYLA treatment and prior to each KADCYLA dose. Patients with known active hepatitis B virus or hepatitis C virus were excluded from EMILIA. Reduce dose or discontinue KADCYLA as appropriate in cases of increased serum transaminases and/or total bilirubin. Permanently discontinue KADCYLA treatment in patients with serum transaminases >3×ULN and concomitant total bilirubin >2×ULN. In clinical trials of KADCYLA, cases of nodular regenerative hyperplasia (NRH) of the liver have been identified from liver biopsies (3 cases out of 884 treated patients, 1 of which was fatal). NRH should be considered in all patients with clinical symptoms of portal hypertension and/or cirrhosis-like pattern seen on the computed tomography scan of the liver but with normal transaminases and no manifestations of cirrhosis. Diagnosis can be confirmed only by histopathology. Upon diagnosis, KADCYLA treatment must be permanently discontinued. Left Ventricular Dysfunction (Boxed WARNING) Patients treated with KADCYLA are at increased risk of developing left ventricular dysfunction (LVD). A decrease of left ventricular ejection fraction (LVEF) to <40% has been observed in patients treated with KADCYLA. In EMILIA, left ventricular dysfunction occurred in 1.8% of patients in the KADCYLA-treated group and 3.3% of patients in the comparator group. Assess LVEF prior to initiation of KADCYLA and at regular intervals (eg, every 3 months) during treatment. Treatment with KADCYLA has not been studied in patients with LVEF <50% prior to treatment. If, at routine monitoring, LVEF is <40%, or is 40% to 45% with a 10% or greater absolute decrease below the pretreatment value, withhold KADCYLA and repeat LVEF assessment within approximately 3 weeks. Permanently discontinue KADCYLA if the LVEF has not improved or has declined further. Embryo-Fetal Toxicity (Boxed WARNING) KADCYLA can cause fetal harm when administered to a pregnant woman. Treatment with trastuzumab, the antibody component of KADCYLA, during pregnancy in the postmarketing setting has resulted in cases of oligohydramnios; oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death were observed in the postmarketing setting in patients treated with trastuzumab. DM1, the cytotoxic component of KADCYLA, can cause embryo-fetal toxicity, based on its mechanism of action. Verify the pregnancy status of women of reproductive potential prior to the initiation of KADCYLA. Advise pregnant women and females of reproductive potential that exposure to KADCYLA during pregnancy or within 7 months prior to conception can result in fetal harm. Advise women of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of KADCYLA. If KADCYLA is administered during pregnancy or if a patient becomes pregnant while receiving KADCYLA or within 7 months following the last dose of KADCYLA, immediately report exposure to the Genentech Adverse Event Line at 1-888-835-25551-888-835-2555. Encourage women who may be exposed to KADCYLA during pregnancy or within 7 months prior to conception, to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720 1-800-690-6720 or visiting http://www.motherpregnancyregistry.com/. Pulmonary Toxicity Cases of interstitial lung disease (ILD), including pneumonitis, some leading to acute respiratory distress syndrome or fatal outcome, have been reported in clinical trials with KADCYLA. Signs and symptoms include dyspnea, cough, fatigue, and pulmonary infiltrates. In EMILIA, the overall frequency of pneumonitis was 1.2%. Treatment with KADCYLA should be permanently discontinued in patients diagnosed with ILD or pneumonitis. Patients with dyspnea at rest due to complications of advanced malignancy and comorbidities may be at increased risk of pulmonary events. Infusion-Related Reactions, Hypersensitivity Reactions Treatment with KADCYLA has not been studied in patients who had trastuzumab permanently discontinued due to infusion-related reactions (IRR) and/or hypersensitivity; treatment with KADCYLA is not recommended for these patients. Infusion-related reactions characterized by one or more of the following symptoms—flushing, chills, pyrexia, dyspnea, hypotension, wheezing, bronchospasm, and tachycardia—have been reported in clinical trials of KADCYLA. In the randomized trial, the overall frequency of IRRs in patients treated with KADCYLA was 1.4%. In most patients, these reactions resolved over the course of several hours to a day after the infusion was terminated. KADCYLA treatment should be interrupted in patients with severe IRRs and permanently discontinued in the event of a life-threatening IRR. Patients should be observed closely for IRRs, especially during the first infusion. One case of a serious, allergic/anaphylactoid-like infusion reaction has been observed in clinical trials of single-agent KADCYLA. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use. Hemorrhage Cases of hemorrhagic events, including central nervous system, respiratory, and gastrointestinal hemorrhage, have been reported in clinical trials with KADCYLA. Some of these bleeding events resulted in fatal outcomes. In EMILIA the incidence of ≥Grade 3 hemorrhage was 1.8% in the KADCYLA-treated group and 0.8% in the comparator group. Although in some of the observed cases the patients were also receiving anticoagulation therapy or antiplatelet therapy, or had thrombocytopenia, in others there were no known additional risk factors. Anticoagulation therapy and antiplatelet agents may increase the risk of bleeding. Use caution with these agents and consider additional monitoring when concomitant use is medically necessary. Thrombocytopenia Thrombocytopenia was reported in clinical trials of KADCYLA. The majority of these patients had Grade 1 or 2 events (<LLN to ≥50,000/mm3), with the nadir occurring by day 8 and generally improving to Grade 0 or 1(≥75,000/mm3) by the next scheduled dose. In clinical trials of KADCYLA, the incidence and severity of thrombocytopenia were higher in Asian patients. In EMILIA, the incidence of≥Grade 3 thrombocytopenia was 14.5% in the KADCYLA-treated group and 0.4% in the comparator group. In Asian patients, the incidence of ≥Grade 3 thrombocytopenia was 45.1% in the KADCYLA group and 1.3% in the comparator group. Monitor platelet counts prior to initiation of KADCYLA and prior to each KADCYLA dose. KADCYLA has not been studied in patients with platelet counts ≤100,000/mm3 prior to initiation of treatment. In the event of decreased platelet count to Grade 3 or greater (<50,000/mm3), do not administer KADCYLA until platelet counts recover to Grade 1 (≥75,000/mm3). Patients with thrombocytopenia(≤100,000/mm3) prior to initiation of KADCYLA and patients on anticoagulant treatment should be closely monitored during treatment with KADCYLA. Neurotoxicity Peripheral neuropathy, mainly as Grade 1 and predominantly sensory, was reported in clinical trials of KADCYLA. In EMILIA, the incidence of ≥Grade 3 peripheral neuropathy was 2.2% in the KADCYLA-treated group and 0.2% in the comparator group. KADCYLA should be temporarily discontinued in patients experiencing Grade 3 or 4 peripheral neuropathy until resolution to ≤Grade 2. Patients should be clinically monitored on an ongoing basis for signs/symptoms of neurotoxicity. HER2 Testing Detection of HER2 protein overexpression or gene amplification is necessary for selection of patients appropriate for KADCYLA therapy, because these are the only patients studied for whom benefit has been shown. Assessment of HER2 status should be done using an FDA-approved test performed by laboratories with demonstrated proficiency. In the randomized study, patients with breast cancer were required to have evidence of HER2 overexpression defined as 3+ IHC and/or FISH amplification ratio ≥2.0 assessed by a validated test. Extravasation In KADCYLA clinical studies, reactions secondary to extravasation have been observed. These reactions, observed more frequently within 24 hours of infusion, were usually mild and comprised erythema, tenderness, skin irritation, pain, or swelling at the infusion site. The infusion site should be closely monitored for possible subcutaneous infiltration during drug administration. Specific treatment for KADCYLA extravasation is unknown. Use in Specific Populations Nursing Mothers There is no information regarding the presence of ado-trastuzumab emtansine in human milk, the effects on the breastfed infant, or the effects on milk production. DM1, the cytotoxic component of KADCYLA, may cause serious adverse reactions in breastfed infants, based on its mechanism of action. Advise women not to breastfeed during treatment and for 7 months following the last dose of KADCYLA. This article Department of pharmacists/medical experts original translation finishing, welcome to reprint! At the same time the procurement of domestic scientific research institutions can contact us: 2363244352.3330889895 -------------------------------------------- 产地国家: 美国 原产地英文商品名: KADCYLA for injection 100MG/vial 原产地英文药品名: ADO﹣TRASTUZUMAB EMTANSINE 中文参考商品译名: KADCYLA冻干粉注射剂 100毫克/支 中文参考药品译名: 曲妥珠单抗 生产厂家中文参考译名: 基因泰克公司 生产厂家英文名: GENENTECH ----------------------------------------------- 产地国家: 美国 原产地英文商品名: KADCYLA for injection 160MG/vial 原产地英文药品名: ADO﹣TRASTUZUMAB EMTANSINE 中文参考商品译名: KADCYLA冻干粉注射剂 160毫克/支 中文参考药品译名: 曲妥珠单抗 生产厂家中文参考译名: 基因泰克公司 生产厂家英文名: GENENTECH ----------------------------------------------- 产地国家: 德国 原产地英文商品名: KADCYLA 100MG/vial 原产地英文药品名: ADO﹣TRASTUZUMAB EMTANSINE 中文参考商品译名: KADCYLA冻干粉注射剂 100毫克/支 中文参考药品译名: 曲妥珠单抗 生产厂家中文参考译名: 基因泰克公司 生产厂家英文名: GENENTECH ----------------------------------------------- 产地国家: 德国 原产地英文商品名: KADCYLA 160MG/vial 原产地英文药品名: ADO﹣TRASTUZUMAB EMTANSINE 中文参考商品译名: KADCYLA冻干粉注射剂 160毫克/支 中文参考药品译名: 曲妥珠单抗 生产厂家中文参考译名: 基因泰克公司 生产厂家英文名: GENENTECH ----------------------------------------------- 产地国家: 日本 原产地英文商品名: KADCYLA  inj 100MG/5mL/vial 原产地英文药品名: ADO﹣TRASTUZUMAB EMTANSINE 中文参考商品译名: KADCYLA冻干粉注射剂 100毫克/5毫升/支 中文参考药品译名: 曲妥珠单抗 生产厂家英文名: Chugai Pharmaceutical Co.Ltd. 生产厂家中文参考译名: 中外制药 ----------------------------------------------- 产地国家: 日本 原产地英文商品名: KADCYLA  inj 160MG/8mLvial 原产地英文药品名: ADO﹣TRASTUZUMAB EMTANSINE 中文参考商品译名: KADCYLA冻干粉注射剂 160毫克/8毫升/支 中文参考药品译名: 曲妥珠单抗 生产厂家英文名: Chugai Pharmaceutical Co.Ltd. 生产厂家中文参考译名: 中外制药