美国FDA批准Perjeta为乳癌新辅助治疗
——被批准的为乳癌手术前第一个药物。
2013年9月30日美国食品和药品监督管理局(FDA)授权加速批准Perjeta(pertuzumab)作为有早期乳癌手术前患者完整治疗方案的一部分(新辅助情况)。Perjeta是被FDA批准第一个为乳癌的新辅助治疗药物。
Perjeta在2012年被批准为有晚期或后期(转移)HER2-阳性乳癌患者的治疗。HER2-阳性乳癌有增加量的HER2蛋白对癌细胞生长和活存有贡献。
Perjeta的新使用是意向为有HER2-阳性，局部晚期，炎症或早期乳癌(肿瘤直径大于2 cm或有阳性淋巴结)处于有癌症回复或播散(转移)或因疾病死亡高风险的患者。它将手术前与曲妥珠单抗[trastuzumab]和其他化疗联用和，取决于所用治疗方案，可能是手术后接着化疗。手术后，患者应继续接受曲妥珠单抗完成一年治疗。
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：“我们正在看到治疗范式显著转变至早期阶段乳癌，”“通过在疾病最早情况高危患者可得到有效治疗，我们可能延缓或阻止癌症复发。”
PERJETATM (pertuzumab)注射剂，静脉使用
批准日期：2012年6月8日；公司：Genentech
作用机制
Pertuzumab靶向细胞外人表皮生长因子受体2蛋白(HER2)的二聚化结构区(子结构区II)，因此，阻断HER2与其它HER家族成员，包括 EGFR，HER3和HER4，配基-依赖性异源二聚化作用。其结果，pertuzumab抑制配体-启动细胞内信号通过两条主要信号通路，丝裂原-激活的蛋白(MAP)激酶和磷酸肌醇3 - 激酶(PI3K)。这些信号通路的抑制分别导致细胞生长停止和凋亡。此外，pertuzumab介导抗体-依赖细胞-介导细胞毒性(ADCC)。
而单独pertuzumab抑制人肿瘤细胞增殖，在HER2-过表达外移植肿瘤模型中pertuzumab和曲妥单抗的联用显着增强抗肿瘤活性。
适应证和用途
PERJETA是一种HER2/neu受体拮抗剂适用于与曲妥单抗[trastuzumab]和多西他奇[docetaxel]联用为未曾接受既往抗-HER2治疗或化疗的HER2-阳性转移乳癌患者为转移疾病的治疗。
剂量和给药方法
（1）只为静脉输注。不要静脉推注或丸注给药。
（2）初始剂量为840 mg历时60-分钟静脉输注。其后每3周420 mg历时30至60分钟静脉输注。
剂型和规格
420mg/14mL单次用小瓶。
禁忌证
无。
警告和注意事项
（1）胚胎-胎儿毒性：但给予妊娠妇女可能发生胎儿危害。
（2）左心室功能不全：监视LVEF和如适当时撤消给药。
（3）输注相关反应, 超敏性反应/过敏反应：监视体征和症状。如发生重要输注-相关反应，减慢或中断输注和给予适当医药治疗。
（4）HER2测试：由证实精通熟练实验室用FDA批准的检验进行。
不良反应
用PERJETA与曲妥单抗和多西他奇联用最常见不良反应(> 30%)是腹泻，脱发，中性细胞减少，恶心，疲乏，皮疹,和周围神经病。
报告怀疑不良反应，联系Genentech电话1-888-835-2555或FDA电话1-800-FDA-1088或www.fda.gov/medwatch.
在特殊人群中使用
（1）哺乳母亲：终止哺乳或终止PERJETA，考虑药物对母亲的重要性。
（2）女性的生殖潜能：忠告女性关于预防妊娠和计划，鼓励患者参加MotHER妊娠注册电话1-800-690-6720联系。
如何供应/贮存和处置
1 如何供应
PERJETA以一个420 mg/14 mL(30 mg/mL)单次用小瓶无防腐剂溶液供应。NDC 50242-145-01.
用前小瓶贮存在冰箱在2°C至8°C(36°F至46°F)。
为了避光保护小瓶在外面纸盒中。
PERJETA Indication and Important Safety Information
INDICATION
PERJETA® (pertuzumab) is a HER2/neu receptor antagonist indicated for:
Treatment of metastatic breast cancer in combination with Herceptin® (trastuzumab) and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease
Use in combination with trastuzumab and docetaxel as neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer. This indication is based on demonstration of an improvement in pathological complete response rate. No data are available demonstrating improvement in event-free survival or overall survival
Limitations of Use:
The safety of PERJETA as part of a doxorubicin-containing regimen has not been established
The safety of PERJETA administered for greater than 6 cycles for early breast cancer has not been established
Important Safety Information
Boxed WARNINGS: Cardiomyopathy and Embryo-Fetal Toxicity
PERJETA administration can result in subclinical and clinical cardiac failure. eva luate left ventricular function in all patients prior to and during treatment with PERJETA. Discontinue PERJETA treatment for a confirmed clinically significant decrease in left ventricular function
Exposure to PERJETA can result in embryo-fetal death and birth defects. Studies in animals have resulted in oligohydramnios, delayed renal development, and death. Advise patients of these risks and the need for effective contraception
Additional Important Safety Information
PERJETA is contraindicated in patients with known hypersensitivity to pertuzumab or to any of its excipients
PERJETA has been associated with infusion and hypersensitivity reactions/anaphylaxis
Detection of HER2 protein overexpression is necessary for selection of patients appropriate for PERJETA therapy
In the treatment of MBC, the most common adverse reactions (>30%) seen with PERJETA in combination with Herceptin and docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy
Most Common Adverse Reactions in Neoadjuvant Treatment of Breast Cancer:
The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and docetaxel were alopecia, diarrhea, nausea, and neutropenia
The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and docetaxel when given for 3 cycles following 3 cycles of FEC were fatigue, alopecia, diarrhea, nausea, vomiting, and neutropenia
The most common adverse reactions (>30%) with PERJETA in combination with docetaxel, carboplatin, and trastuzumab (TCH) were fatigue, alopecia, diarrhea, nausea, vomiting, neutropenia, thrombocytopenia, and anemia
You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
You may also report side effects to Genentech at 1-888-835-2555
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20142919453433.pdf