Phase II Randomized Study of Trastuzumab Emtansine Versus Trastuzumab Plus Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer
Phase II Randomized Study of Trastuzumab Emtansine Versus Trastuzumab Plus Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer
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DOI：
10.1200/jco.2012.44.9694
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发表时间：
2013-03-20
影响因子：
45.3
通讯作者：
Perez, Edith A.
中科院分区：
文献类型：
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作者：
Hurvitz, Sara A.;Dirix, Luc;Perez, Edith A.
目的曲妥珠单抗 emtansine (T-DM1) 是一种抗体药物缀合物，由细胞毒性剂 DM1 通过稳定的硫醚连接体与曲妥珠单抗缀合而成，在招募患有人表皮生长因子受体 2 (HER2) 阳性转移性乳腺癌 (MBC) 且疾病已进展的患者的单组研究中显示出临床活性。 转移性环境中的 HER2 靶向治疗。 患者和方法 HER2 阳性 MBC 或复发性局部晚期乳腺癌患者 (N = 137) 被随机分配至曲妥珠单抗加多西他赛 (HT；n = 70) 或 T-DM1 (n = 67) 作为一线治疗，直至疾病进展或出现不可接受的毒性。主要终点是研究者评估的无进展生存期（PFS）和安全性。关键的次要终点包括总生存期 (OS)、客观缓解率 (ORR)、客观缓解持续时间、临床受益率和生活质量。 结果 HT 组的中位 PFS 为 9.2 个月，T-DM1 组的中位 PFS 为 14.2 个月（风险比，0.59；95% CI，0.36 至 0.97）；两组的中位随访时间约为 14 个月。 HT 组的 ORR 为 58.0%（95% CI，45.5% 至 69.2%），T-DM1 组的 ORR 为 64.2%（95% CI，51.8% 至 74.8%）。与 HT 相比，T-DM1 具有良好的安全性，≥3 级不良事件（AE；46.4% vs 90.9%）、导致治疗中断的 AE（7.2% vs 40.9%）和严重 AE（20.3% vs 25.8%）较少。治疗组之间的初步 OS 结果相似；两组的中位随访时间约为 23 个月。 结论 在这项随机 II 期研究中，与 HT 相比，T-DM1 一线治疗 HER2 阳性 MBC 患者的 PFS 显着改善，且安全性良好。 J 临床肿瘤杂志 31：1157-1163。 (C) 2013 年美国临床肿瘤学会
PurposeTrastuzumab emtansine (T-DM1), an antibody-drug conjugate composed of the cytotoxic agent DM1 conjugated to trastuzumab via a stable thioether linker, has shown clinical activity in single-arm studies enrolling patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) whose disease had progressed on HER2-targeted therapy in the metastatic setting.Patients and MethodsPatients (N = 137) with HER2-positive MBC or recurrent locally advanced breast cancer were randomly assigned to trastuzumab plus docetaxel (HT; n = 70) or T-DM1 (n = 67) as first-line treatment until disease progression or unacceptable toxicity. Primary end points were investigator-assessed progression-free survival (PFS) and safety. Key secondary end points included overall survival (OS), objective response rate (ORR), duration of objective response, clinical benefit rate, and quality of life.ResultsMedian PFS was 9.2 months with HT and 14.2 months with T-DM1 (hazard ratio, 0.59; 95% CI, 0.36 to 0.97); median follow-up was approximately 14 months in both arms. ORR was 58.0% (95% CI, 45.5% to 69.2%) with HT and 64.2% (95% CI, 51.8% to 74.8%) with T-DM1. T-DM1 had a favorable safety profile versus HT, with fewer grade >= 3 adverse events (AEs; 46.4% v 90.9%), AEs leading to treatment discontinuations (7.2% v 40.9%), and serious AEs (20.3% v 25.8%). Preliminary OS results were similar between treatment arms; median follow-up was approximately 23 months in both arms.ConclusionIn this randomized phase II study, first-line treatment with T-DM1 for patients with HER2-positive MBC provided a significant improvement in PFS, with a favorable safety profile, versus HT. J Clin Oncol 31:1157-1163. (C) 2013 by American Society of Clinical Oncology