Department of Pharmacy, Lyndon B. Johnson General Hospital, Harris Health System, Houston, TX 77026, USA.
Am J Health Syst Pharm. 2013 Sep 15;70(18):1579-87. doi: 10.2146/ajhp120735.
The pharmacology, pharmacokinetics, clinical efficacy, safety, and administration of pertuzumab in patients with metastatic human epidermal growth factor receptor type 2 (HER2)-positive breast cancer are reviewed.
Disease progression in HER2-positive breast cancer is often due to resistance to or a lack of efficacy of trastuzumab-based anti-HER2 therapy. Pertuzumab is the first humanized monoclonal antibody in a new class of drugs, the HER dimerization inhibitors, approved by the Food and Drug Administration for the first-line treatment of patients with metastatic HER2-positive breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. Since pertuzumab binds to a different epitope than trastuzumab, combination therapy with pertuzumab and trastuzumab results in a more complete blockade of HER2 signaling than trastuzumab monotherapy. The efficacy of adding pertuzumab to trastuzumab-docetaxel dual therapy was demonstrated in a pivotal randomized multicenter Phase III trial, which showed a significant benefit in terms of progression-free survival, with improved overall survival, in favor of the triple therapy as an initial regimen in treatment-naive patients with metastatic HER2-positive breast cancer. The combination of pertuzumab and trastuzumab has been found to have a tolerable toxicity profile. As clinical trials of pertuzumab for adjuvant, neoadjuvant, and metastatic-disease treatment continue, its role in the treatment of HER2-positive breast cancer will continue to evolve.
Pertuzumab, a novel HER2 dimerization inhibitor, has been shown to be effective in the treatment of metastatic HER2-positive breast cancer when used in combination with trastuzumab and docetaxel and is recommended for first-line therapy.
综述曲妥珠单抗治疗转移性人表皮生长因子受体 2（HER2）阳性乳腺癌患者的药理学、药代动力学、临床疗效、安全性和给药方法。
HER2 阳性乳腺癌的疾病进展通常是由于对曲妥珠单抗为基础的抗 HER2 治疗产生耐药或疗效不足所致。帕妥珠单抗是首个获得美国食品和药物管理局批准的新型药物——HER 二聚体抑制剂类药物中的人源化单克隆抗体，用于治疗未曾接受过抗 HER2 治疗或转移性疾病化疗的转移性 HER2 阳性乳腺癌患者的一线治疗。由于帕妥珠单抗与曲妥珠单抗结合的表位不同，与曲妥珠单抗联合用药可更完全阻断 HER2 信号，优于曲妥珠单抗单药治疗。一项关键性随机多中心 III 期试验表明，帕妥珠单抗联合曲妥珠单抗-多西他赛双药治疗可显著提高无进展生存期，且总体生存获益更优，从而支持将三药联合方案作为治疗初治转移性 HER2 阳性乳腺癌患者的初始方案。帕妥珠单抗联合曲妥珠单抗的毒性可耐受。随着帕妥珠单抗在辅助治疗、新辅助治疗和转移性疾病治疗的临床试验不断开展，其在 HER2 阳性乳腺癌治疗中的作用将不断演变。
新型 HER2 二聚体抑制剂帕妥珠单抗与曲妥珠单抗和多西他赛联合应用治疗转移性 HER2 阳性乳腺癌显示出有效性，推荐用于一线治疗。
