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曲妥珠单抗和帕妥珠单抗联合每周一次紫杉醇治疗HER2过表达转移性乳腺癌患者:一项II期研究的总生存和更新的无进展生存结果

Weekly paclitaxel with trastuzumab and pertuzumab in patients with HER2-overexpressing metastatic breast cancer: overall survival and updated progression-free survival results from a phase II study.

作者信息

Smyth L M, Iyengar N M, Chen M F, Popper S M, Patil S, Wasserheit-Lieblich C, Argolo D F, Singh J C, Chandarlapaty S, Sugarman S M, Comen E A, Drullinsky P R, Traina T A, Troso-Sandoval T, Baselga J, Norton L, Hudis C A, Dang C T

机构信息

Breast Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, 300 E 66th St, New York, NY, 10065, USA.

Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, USA.

出版信息

Breast Cancer Res Treat. 2016 Jul;158(1):91-97. doi: 10.1007/s10549-016-3851-7. Epub 2016 Jun 15.

Abstract

We previously reported progression-free survival (PFS) results on a phase II trial of weekly paclitaxel, trastuzumab, and pertuzumab in patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer (MBC) treated in the first- and second-line setting. Here, we report results for overall survival (OS) and updated PFS after an additional year of follow-up. Patients with HER2-positive MBC with 0-1 prior treatment were eligible. Treatment consisted of paclitaxel (80 mg/m(2)) weekly, and trastuzumab (loading dose 8 mg/kg → 6 mg/kg) and pertuzumab (loading dose 840 mg → 420 mg) every 3 weeks, all given intravenously. Primary endpoint was 6-month PFS. Secondary endpoints included median PFS, 6-month and median OS. Evaluable patients received at least one full dose of treatment. From January 2011 to December 2013, 69 patients were enrolled: 51 (74 %) and 18 (26 %) treated in first- and second-line metastatic settings, respectively. As of July 1, 2015, the median follow-up was 33 months (range 3-49 months; 67 patients were evaluable for efficacy). The median OS was 44 months (95 % CI 37.5-NR) overall and 44 months (95 % CI 38.3-NR) and 37.5 months (95 % CI 30.3-NR) for patients with 0 and 1 prior metastatic treatment, respectively; 6-month OS was 98 % (95 % CI 90-1). The 6-month PFS was 86 % (95 % CI 75-93) overall and 89 % (95 % CI 76-95) and 78 % (95 % CI 51-91) for patients with 0 and 1 prior therapy, respectively; and median PFS was 21.4 months (95 % CI 14.1-NR) overall and 25.7 months (95 % CI 14.1-NR) and 16.9 months (95 % CI 8.5-NR) for patients with 0-1 prior treatment, respectively. Treatment was well tolerated. Updated analysis demonstrates that weekly paclitaxel, when added to trastuzumab and pertuzumab, is associated with a favorable OS and PFS and offers an alternative to docetaxel-based therapy. http://www.ClinicalTrials.gov NCT0127604.

摘要

我们之前报告了一项II期试验的无进展生存期(PFS)结果,该试验针对一线和二线治疗的人表皮生长因子受体2(HER2)阳性转移性乳腺癌(MBC)患者,采用每周一次紫杉醇、曲妥珠单抗和帕妥珠单抗治疗。在此,我们报告额外一年随访后的总生存期(OS)结果及更新的PFS结果。HER2阳性MBC且既往接受0 - 1次治疗的患者符合入组条件。治疗方案为每周静脉注射紫杉醇(80mg/m²),每3周静脉注射曲妥珠单抗(负荷剂量8mg/kg→6mg/kg)和帕妥珠单抗(负荷剂量840mg→420mg)。主要终点为6个月PFS。次要终点包括中位PFS、6个月和中位OS。可评估患者接受了至少一剂完整治疗。2011年1月至2013年12月,共入组69例患者:分别有51例(74%)和18例(26%)在一线和二线转移性治疗中接受治疗。截至2015年7月1日,中位随访时间为33个月(范围3 - 49个月;67例患者可评估疗效)。总体中位OS为44个月(95%CI 37.5 - NR),既往有0次和1次转移性治疗的患者中位OS分别为44个月(95%CI 38.3 - NR)和37.5个月(95%CI 30.3 - NR);6个月OS为98%(95%CI 90 - 1)。总体6个月PFS为86%(95%CI 75 - 93),既往有0次和1次治疗的患者6个月PFS分别为89%(95%CI 76 - 95)和78%(95%CI 51 - 91);总体中位PFS为21.4个月(95%CI 14.1 - NR),既往接受0 - 1次治疗的患者中位PFS分别为25.7个月(95%CI 14.1 - NR)和16.9个月(95%CI 8.5 - NR)。治疗耐受性良好。更新分析表明,在曲妥珠单抗和帕妥珠单抗基础上加用每周一次紫杉醇与良好的OS和PFS相关,为基于多西他赛的治疗提供了一种替代方案。http://www.ClinicalTrials.gov NCT0127604

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