Clemens Michael R, Gladkov Oleg A, Gartner Elaina, Vladimirov Vladimir, Crown John, Steinberg Joyce, Jie Fei, Keating Anne
Innere Medizin I, Klinikum Mutterhaus de Borromaerinnen GmbH, Trier, Germany,
Breast Cancer Res Treat. 2015 Jan;149(1):171-9. doi: 10.1007/s10549-014-3238-6. Epub 2014 Dec 30.
The objective of this study was to assess the efficacy and tolerability of YM155, a survivin suppressor, in combination with docetaxel, compared with docetaxel alone in patients with HER2-negative metastatic breast cancer. This phase II, multicenter, open-label, 2-arm study randomized patients (≥18 years) with histologically or cytologically confirmed stage IV HER2-negative metastatic breast cancer and ≥1 measurable lesion, to receive docetaxel alone or docetaxel plus YM155. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), duration of response (DOR), clinical benefit rate (CBR), time to response (TTR), biomarker assessment, and analysis of circulating tumor cells. Patients were women diagnosed with HER2-negative breast cancer; most had received prior drug therapies. The median PFS was 8.4 months with YM155 plus docetaxel (n = 50) and 10.5 months with docetaxel alone (n = 51; HR 1.53; 95 % CI 0.83, 2.83; P = 0.176). No statistically significant differences were observed for secondary endpoints, although slightly greater OS (630 vs 601 days; P = 0.768), CBR (84.3 vs 82.0 %; P = 0.855), DOR, and TTR were observed with docetaxel alone compared with YM155 plus docetaxel, whereas ORR was similar (25.5 vs 26.0). The most common TEAEs observed with YM155 plus docetaxel compared with docetaxel alone were neutropenia (83.3 vs 84.3 %), alopecia (62.5 vs 52.9 %), fatigue (50 vs 41.2 %), and nausea (37.5 vs 41.2 %). Although YM155 is a novel drug that suppresses survivin, YM155 plus docetaxel exhibited no statistically significant differences in endpoints compared with docetaxel alone. The combination regimen was well tolerated.
本研究的目的是评估生存素抑制剂YM155联合多西他赛与多西他赛单药治疗HER2阴性转移性乳腺癌患者的疗效和耐受性。这项II期、多中心、开放标签、双臂研究将年龄≥18岁、组织学或细胞学确诊为IV期HER2阴性转移性乳腺癌且有≥1个可测量病灶的患者随机分为两组，分别接受多西他赛单药治疗或多西他赛加YM155治疗。主要终点为无进展生存期（PFS）。次要终点包括客观缓解率（ORR）、总生存期（OS）、缓解持续时间（DOR）、临床获益率（CBR）、缓解时间（TTR）、生物标志物评估以及循环肿瘤细胞分析。患者均为诊断为HER2阴性乳腺癌的女性；大多数患者之前接受过药物治疗。YM155联合多西他赛组（n = 50）的中位PFS为8.4个月，多西他赛单药组（n = 51）为10.5个月（风险比1.53；95%置信区间0.8, 2.83；P = 0.176）。次要终点未观察到统计学显著差异，尽管单药多西他赛组的总生存期略长（630天对601天；P = 0.768）、临床获益率略高（84.3%对82.0%；P = 0.855）、缓解持续时间和缓解时间更长，而客观缓解率相似（25.5%对26.0%）。与多西他赛单药治疗相比，YM155联合多西他赛治疗最常见的治疗中出现的不良事件为中性粒细胞减少（83.3%对84.3%）、脱发（62.5%对52.9%）、疲劳（50%对41.2%）和恶心（37.5%对41.2%）。尽管YM155是一种新型的生存素抑制药物，但与多西他赛单药治疗相比，YM155联合多西他赛在各终点上未显示出统计学显著差异。联合治疗方案耐受性良好。
