Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1354, Houston, TX 77030-4009, USA.
Breast Cancer Res Treat. 2010 Jul;122(2):409-18. doi: 10.1007/s10549-010-0901-4. Epub 2010 May 8.
Limited proven treatment options exist for patients with metastatic breast cancer (MBC) resistant to anthracycline and taxane treatment. Ixabepilone, a novel semisynthetic analog of epothilone B, has demonstrated single-agent activity in MBC resistant to anthracyclines and taxanes. In combination with capecitabine in a phase III trial (CA163-046) in this setting, ixabepilone prolonged progression-free survival and increased objective response rate relative to capecitabine (Thomas et al. J Clin Oncol 25:5210-5217, 2007). Here, we report the results of overall survival (OS), a secondary efficacy endpoint from the CA163-046 trial. Seven hundred fifty-two patients with MBC resistant to anthracyclines and taxanes were randomized to ixabepilone (40 mg/m(2) intravenously on day 1 of a 21-day cycle) plus capecitabine (2,000 mg/m(2) orally on days 1 through 14 of a 21-day cycle) or capecitabine alone (2,500 mg/m(2) on the same schedule). Patients receiving ixabepilone plus capecitabine treatment had a median survival of 12.9 months compared to 11.1 months for patients receiving capecitabine alone (HR = 0.9; 95%CI: 077-1.05; P = 0.19). This observed increase in median OS favored the combination; however, the difference was not statistically significant. Predefined subset analyses showed a clinically meaningful increase in OS in KPS 70-80 patients receiving ixabepilone plus capecitabine (HR = 0.75; 95% CI: 0.58-0.98). Ixabepilone plus capecitabine did not show a significant improvement in survival compared to capecitabine alone in patients with MBC resistant to anthracyclines and taxanes. The observed differences in survival favored the combination arm. A clinical benefit was also seen in patients in the KPS 70-80 subgroup.
对于接受蒽环类和紫杉烷类药物治疗耐药的转移性乳腺癌（MBC）患者，现有的治疗选择有限。伊沙匹隆是一种新型半合成埃博霉素 B 类似物，在接受蒽环类和紫杉烷类药物治疗耐药的 MBC 患者中表现出单药活性。在该环境中进行的 III 期试验（CA163-046）中，与卡培他滨联合使用，伊沙匹隆延长了无进展生存期，并提高了客观缓解率，与卡培他滨相比（Thomas 等人，J Clin Oncol 25:5210-5217, 2007）。在这里，我们报告了总生存期（OS）的结果，这是 CA163-046 试验的次要疗效终点。752 名接受蒽环类和紫杉烷类药物治疗耐药的 MBC 患者被随机分配至伊沙匹隆（40mg/m(2)静脉输注，每 21 天周期的第 1 天）+卡培他滨（2000mg/m(2)口服，每 21 天周期的第 1 天至第 14 天）或卡培他滨单药治疗（2500mg/m(2)，相同方案）。接受伊沙匹隆+卡培他滨治疗的患者中位生存期为 12.9 个月，而接受卡培他滨单药治疗的患者中位生存期为 11.1 个月（HR=0.9；95%CI：0.77-1.05；P=0.19）。观察到的中位 OS 延长有利于联合治疗；然而，差异无统计学意义。预先设定的亚组分析显示，在接受伊沙匹隆+卡培他滨治疗的 KPS 70-80 患者中，OS 有临床意义的增加（HR=0.75；95%CI：0.58-0.98）。在接受蒽环类和紫杉烷类药物治疗耐药的 MBC 患者中，与卡培他滨单药治疗相比，伊沙匹隆+卡培他滨治疗并未显著改善生存。在 KPS 70-80 亚组患者中，也观察到生存获益偏向联合治疗组。在临床受益方面，在 KPS 70-80 亚组中也观察到了。
