注射用KADCYLA™ (ado-曲妥珠单抗emtansine)，为静脉使用
美国初始批准：{YYYY}
KADCYLA
Generic Name and Formulations:
Ado-trastuzumab emtansine 100mg, 160mg; per vial; powder; for IV infusion after reconstitution.
适应证和用途
KADCYLA是一种靶向HER2抗体和微管抑制剂结合物适用于，作为单药，为有HER2-阳性，转移乳癌，既往接受曲妥珠单抗和一种紫衫烷类，分开或联合应用患者的治疗。患者应有以下任一情况：
（1）对转移疾病以前接受治疗，或
（2）完成辅助治疗期间或6个月内疾病复发。
剂量和给药方法
（1）只为静脉输注。不要静推注或丸注。不要使用葡萄糖(5%)溶液。
（2）KADCYLA的推荐剂量是3.6 mg/kg每3周(21-天周期)静脉输注给药直至疾病进展或不能接受毒性。不要给予剂量大于3.6 mg/kg的KADCYLA。不要替代KADCYLA或用曲妥珠单抗。
（3）不良事件的处理(输注相关反应，肝毒性，左心室功能障碍，血小板减少，肺毒性或周围神经病变)可能需要暂时中断，减低剂量，或终止KADCYLA治疗。
剂型和规格
在单次使用小瓶冻干粉含100mg每小瓶或160mg每小瓶.
禁忌证
无。
警告和注意事项
（1）肺毒性：在被诊断有间质性肺病或肺炎患者中永久终止KADCYLA。
（2）输注相关反应，超敏性反应：输注期间和后监视体征和症状。如发生重要输注相关反应或超敏性反应，减慢或中断输注和给予适当医学治疗。对危及生命输注相关反应永久终止KADCYLA。
（3）血小板减少：每次给予KADCYLA前监视血小板计数。适当时调整剂量。
（4）神经毒性：监视体征和症状。对经受3或4级周围神经病变患者暂时不用给药。
（5）HER2检验：由有测试能力的实验室用FDA-批准的检验进行检验。
不良反应
用KADCYLA (n=884被治疗患者)最常见不良反应(频数> 25%)是疲乏，恶心，肌肉骨骼痛，血小板减少，头痛，转氨酶增加，和便秘。
在特殊人群中使用
（1）哺乳母亲：终止哺乳或终止KADCYLA考虑到药物对母亲的重要性。
（2）生殖潜能妇女：忠告女性关于预防和计划妊娠。
Company:
Genentech, Inc.
Indications for KADCYLA:
Treatment in patients with HER2-positive (+), 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
6 months of completing adjuvant therapy.
Adult Dose for KADCYLA:
Give by IV infusion only over 90 minutes 3.6mg/kg max every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity. Subsequent infusions may be given over 30 minutes if previously tolerated. Monitor closely for possible SC infiltration during infusion. Dose modifications: see full labeling.
Children's Dose for KADCYLA:
Not established.
Pharmacological Class:
HER2-targeted antibody-drug conjugate.
Warnings/Precautions:
Do not substitute for or with trastuzumab. Hepatotoxicity; monitor serum transaminases and bilirubin prior to starting and to each dose; reduce dose or discontinue if occurs. Risk of left ventricular dysfunction. Assess LVEF prior to initiation and every 3 months during treatment; interrupt and discontinue as appropriate. Risk of embryo-fetal toxicity. Permanently discontinue if interstitial lung disease or pneumonitis occurs. Monitor for signs/symptoms of extravasation, infusion-related or hypersensitivity reactions; if significant, slow or interrupt infusion; discontinue if life-threatening. Monitor platelets at baseline and prior to each dose; if platelets <50,000/mm3, delay dose until recovery to ≥75,000/mm3; if platelets <25,000/mm3, delay until recovery to ≥75,000/mm3 and reduce dose. If thrombocytopenia occurs <100,000/mm3 and concomitant anticoagulants, monitor closely. Monitor for neurotoxicity; withhold temporarily if Grade 3 or 4 peripheral neuropathy occurs. Test for HER2 protein overexpression or gene amplification using FDA-approved tests by labs with demonstrated proficiency. Pregnancy (Category D); use adequate contraception during and at least 6 months after last dose. Nursing mothers: not recommended.
Interactions:
Avoid concomitant strong CYP3A4 inhibitors (eg, azole antifungals, clarithromycin, atazanavir, indinavir, ritonavir, nefazodone, nelfinavir, saquinavir, telithromycin); if unavoidable, consider delaying therapy (see full labeling).
Adverse Reactions:
Fatigue, nausea, musculoskeletal pain, thrombocytopenia, headache; increased transaminases, constipation.
Generic Availability:
NO
How Supplied:
Single-use vial—1
批准日期：2013年2月22日；公司：Genentech，Inc.
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。”
优先审评
Kadcyla Approved for Metastatic Breast Cancer
KADCYLA (ado-trastuzumab emtansine) ImmunoGen announced that Genentech has reported the FDA approval of Kadcyla (ado-trastuzumab emtansine) for the treatment of HER2-positive metastatic breast cancer in patients who have received prior treatment with Herceptin (trastuzumab; Genentech) and a taxane chemotherapy.
Ado-trastuzumab emtansine is an antibody-drug conjugate (ADC) comprised of the antibody trastuzumab and the chemotherapy DM1 attached together using a stable linker. It is designed to target and inhibit HER2 signaling and deliver the chemotherapy directly inside HER2-positive cancer cells.
Kadcyla was granted priority review on November 2012. Genentech plans to launch Kadcyla soon.
FDA批准HER-2阳性乳腺癌治疗新药上市
2013年2月22日，美国食品与药物管理局（FDA）通过优先审查程序批准了Kadcyla(ado-trastuzumab emtansine)用于治疗人表皮生长因子受体2( HER-2) 阳性晚期（转移性）乳腺癌患者。
Kadcyla预期用于之前接受过曲妥珠单抗，其他抗HER2阳性疗法和紫杉烷类治疗的乳腺癌患者。Kadcyla通过将曲妥珠单抗和DM1结合来干预肿瘤细胞的生长，是FDA批准的第4个靶向HER-2蛋白药物。其他3种获准治疗HER-2阳性乳腺癌药物分别为曲妥珠单抗（1998），拉帕替尼（lapatinib，2007）和帕妥珠单抗（Pertuzumab，2012）。
在临床试验过程中，Kadcyla被称为T-DM1。一项纳入991例患者的临床试验评估了Kadcyla的安全性和有效性。这些受试者被随机分为接受Kadcyla治疗组和拉帕替尼联合卡培他滨治疗组。治疗直到肿瘤进展或出现不耐受的不良反应。评估患者的无进展生存期，总生存和死亡前生存时间。
结果显示，中位无进展生存期在Kadcyla治疗组为9.6个月，在拉帕替尼联合卡培他滨治疗组为6.4个月。中位总体生存在Kadcyla治疗组为30.9个月，在拉帕替尼联合卡培他滨治疗组为25.1个月。
Kadcyla有一项加框警告提醒医务人员和患者，该药可导致肝损害，心脏毒性和死亡。它还能导致严重致命的出生缺陷，因此女性在启动Kadcyla治疗前应排除妊娠。
接受Kadcyla治疗的患者最常见不良反应为恶心，疲乏，肌痛和关节痛，血小板减少，肝酶水平升高，头痛和便秘。
乳腺癌是妇女第二大癌症相关死亡原因。根据美国国家癌症研究所提供的数据，估计2013年美国将有232340名妇女被诊断患有乳腺癌，39620名患者将死于乳腺癌。近20%乳腺癌患者的HER2蛋白数量扩增。