FDA Approval: Ado-Trastuzumab Emtansine for the Treatment of Patients with HER2-Positive Metastatic Breast Cancer
FDA Approval: Ado-Trastuzumab Emtansine for the Treatment of Patients with HER2-Positive Metastatic Breast Cancer
复制标题
DOI：
10.1158/1078-0432.ccr-14-0012
复制
发表时间：
2014-09-01
影响因子：
11.5
通讯作者：
Cortazar, Patricia
中科院分区：
文献类型：
--
作者：
Amiri-Kordestani, Laleh;Blumenthal, Gideon M.;Cortazar, Patricia
2013年2月22日，FDA批准了ado-trastuzumab emtansine(Kadcyla；Genentech，Inc.)作为单一药物用于治疗人表皮生长因子受体2(HER2)阳性转移性乳腺癌(MBC)患者，这些患者以前单独或联合接受曲妥珠单抗和紫杉烷治疗。许可的临床基础是在991名HER2阳性的MBC患者中进行的III期试验，该试验随机分配患者接受阿曲珠单抗恩坦辛(n=495)或拉帕替尼与卡培他滨联合治疗(n=496)。盆腔终点是基于独立审查委员会的肿瘤评估和总生存率(OS)的无进展生存期(PFS)。接受阿曲珠单抗治疗的患者与接受拉帕替尼和卡培他滨治疗的患者相比，PFS和OS有显著改善[PFS中位数3.2月，HR，0.65(95%可信区间，0.55-0.77)，P<；0.0001，OS中位数5.8月，HR，0.68(95%可信区间，0.55-0.85)，P=0.0006]。接受阿曲曲珠单抗治疗的患者最常见的不良反应是乏力、恶心、肌肉骨骼疼痛、血小板减少、头痛、转氨酶水平升高和便秘。其他明显的不良反应包括肝胆疾病和左心功能不全。考虑到PFS和OS的结果，收益-风险概况被认为是有利的。(C)2014年AACR。
On February 22, 2013, the FDA licensed ado-trastuzumab emtansine (Kadcyla; Genentech, Inc.) for use as a single agent for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) who previously received trastuzumab and a taxane, separately or in combination. The clinical basis for licensure was a phase III trial in 991 patients with HER2-positive MBC that randomly allocated patients to receive ado-trastuzumab emtansine (n = 495) or lapatinib in combination with capecitabine (n 496). The coprimary endpoints were progression-free survival (PFS) based on tumor assessments by an independent review committee and overall survival (OS). Statistically significant improvements in PFS and OS were observed in patients receiving ado-trastuzumab emtansine compared with patients receiving lapatinib plus capecitabine [ difference in PFS medians of 3.2 months, HR, 0.65 (95% confidence interval, CI, 0.55-0.77), P < 0.0001 and difference in OS medians of 5.8 months, HR, 0.68 (95% CI, 0.55-0.85), P = 0.0006]. The most common adverse reactions in patients receiving adotrastuzumab emtansine were fatigue, nausea, musculoskeletal pain, thrombocytopenia, headache, increased aminotransferase levels, and constipation. Other significant adverse reactions included hepatobiliary disorders and left ventricular dysfunction. Given the PFS and OS results, the benefit-risk profile was considered favorable. (C) 2014 AACR.