First FDA Approval of Neoadjuvant Therapy for Breast Cancer: Pertuzumab for the Treatment of Patients with HER2-Positive Breast Cancer
First FDA Approval of Neoadjuvant Therapy for Breast Cancer: Pertuzumab for the Treatment of Patients with HER2-Positive Breast Cancer
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DOI：
10.1158/1078-0432.ccr-14-1268
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发表时间：
2014-11-01
影响因子：
11.5
通讯作者：
Cortazar, Patricia
中科院分区：
文献类型：
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作者：
Amiri-Kordestani, Laleh;Wedam, Suparna;Cortazar, Patricia
2013年9月30日，FDA批准帕妥珠单抗（Perjecta; Genentech，Inc.）作为早期乳腺癌完整治疗方案的一部分，与曲妥珠单抗和多西他赛联合用于HER 2阳性、局部晚期、炎性或早期乳腺癌（直径大于2 cm或淋巴结阳性）患者的新辅助治疗。该批准部分基于在指定人群中进行的一项随机多中心试验，该试验将417例患者分配至曲妥珠单抗-多西他赛（TD）、帕妥珠单抗-曲妥珠单抗-多西他赛（PTD）、帕妥珠单抗-曲妥珠单抗或帕妥珠单抗-多西他赛的新辅助治疗。术前每3周一次给予PTD，共4个周期。手术后，患者接受3个周期的5-氟尿嘧啶、表阿霉素和环磷酰胺（每3周一次）和曲妥珠单抗（每3周一次），以完成1年的治疗。PTD组和TD组的病理学完全缓解率（根据FDA首选定义[乳腺和淋巴结无浸润性癌（ypT 0/is ypN 0）]）分别为39.3%和21.5%（P = 0.0063）。PTD最常见的不良反应是脱发、腹泻、恶心和中性粒细胞减少。这一批准是基于全部证据，特别是转移性乳腺癌试验中改善的生存率，以及完全累积的确证性试验。(C)2014年AACR。
On September 30, 2013, the FDA granted accelerated approval to pertuzumab (Perjecta; Genentech, Inc.) for 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. The approval was based in part on a randomized multicenter trial in the indicated population that allocated 417 patients to neoadjuvant treatment with trastuzumab-docetaxel (TD), pertuzumab-trastuzumab-docetaxel (PTD), pertuzumab-trastuzumab, or pertuzumab-docetaxel. PTD was administered preoperatively every 3 weeks for four cycles. Following surgery patients received three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide every 3 weeks and trastuzumab every 3 weeks to complete 1 year of therapy. The pathologic complete response rates by the FDA-preferred definition [absence of invasive cancer in the breast and lymph nodes (ypT0/is ypN0)] were 39.3% and 21.5% in the PTD and the TD arms, respectively (P = 0.0063). The most common adverse reactions with PTD were alopecia, diarrhea, nausea, and neutropenia. This approval was based on the totality of evidence, particularly improved survival in the metastatic breast cancer trial, and a fully accrued confirmatory trial. (C) 2014 AACR.