European Medicines Agency, London, United Kingdom; Danish Health and Medicines Authority, København, Denmark; Department of Physiology and Pharmacology, Università di Roma "La Sapienza," Rome, Italy; Agenzia Italiana del Farmaco, Rome, Italy; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Karolinska Institutet, Stockholm, Sweden; The Netherlands Cancer Institute, Amsterdam, The Netherlands
European Medicines Agency, London, United Kingdom; Danish Health and Medicines Authority, København, Denmark; Department of Physiology and Pharmacology, Università di Roma "La Sapienza," Rome, Italy; Agenzia Italiana del Farmaco, Rome, Italy; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Karolinska Institutet, Stockholm, Sweden; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Oncologist. 2014 Jul;19(7):766-73. doi: 10.1634/theoncologist.2013-0348. Epub 2014 Jun 13.
Pertuzumab is a recombinant humanized monoclonal antibody that specifically targets the extracellular dimerization domain (subdomain II) of HER2. Based on the positive opinion from the European Medicines Agency (EMA) on March 4, 2013, a marketing authorization valid throughout the European Union (EU) was issued for pertuzumab (Perjeta) for use in combination with trastuzumab and docetaxel for the treatment of adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer who have not received previous anti-HER2 therapy or chemotherapy for their metastatic disease. The demonstration of clinical benefit for pertuzumab was based on a single, phase III, randomized, double-blind, placebo-controlled trial comparing the efficacy and safety of pertuzumab plus trastuzumab plus docetaxel versus placebo plus trastuzumab plus docetaxel in previously untreated patients with locally advanced or metastatic HER2-positive breast cancer. In the primary analysis, median progression-free survival was 18.5 months in the pertuzumab group compared with 12.4 months in the placebo group (hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.51-0.75; p < .0001). For the secondary endpoints, overall survival (HR: 0.66; 95% CI: 0.52-0.84; p = .0008) and objective response rate (80.2% vs. 69.3%) were also favored in the pertuzumab group. Toxicity was similar between groups except for higher incidence of diarrhea, rash, mucosal inflammation, dry skin, and neutropenia for pertuzumab compared with placebo. This paper summarizes the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the EMA website (http://www.ema.europa.eu).
帕妥珠单抗是一种重组人源化单克隆抗体，特异性靶向 HER2 的细胞外二聚化结构域（亚结构域 II）。基于 2013 年 3 月 4 日欧洲药品管理局（EMA）的积极意见，帕妥珠单抗（Perjeta）获得了在整个欧盟（EU）上市许可，可与曲妥珠单抗和多西他赛联合用于治疗未接受过先前抗 HER2 治疗或转移性疾病化疗的 HER2 阳性转移性或局部复发性不可切除乳腺癌成人患者。帕妥珠单抗的临床获益证明是基于一项单臂、III 期、随机、双盲、安慰剂对照临床试验，比较了帕妥珠单抗联合曲妥珠单抗和多西他赛与安慰剂联合曲妥珠单抗和多西他赛在未经治疗的局部晚期或转移性 HER2 阳性乳腺癌患者中的疗效和安全性。在主要分析中，帕妥珠单抗组的中位无进展生存期为 18.5 个月，安慰剂组为 12.4 个月（风险比[HR]：0.62；95%置信区间[CI]：0.51-0.75；p <.0001）。对于次要终点，帕妥珠单抗组的总生存期（HR：0.66；95%CI：0.52-0.84；p =.0008）和客观缓解率（80.2% vs. 69.3%）也有优势。两组的毒性反应相似，但帕妥珠单抗组腹泻、皮疹、粘膜炎症、皮肤干燥和中性粒细胞减少的发生率高于安慰剂组。本文总结了在欧盟批准应用的科学审查。详细的科学评估报告和产品信息，包括产品特性摘要，可在 EMA 网站（http://www.ema.europa.eu）上获取。
