Phase II study of efficacy, safety, and pharmacokinetics of trastuzumab monotherapy administered on a 3-weekly schedule
Phase II study of efficacy, safety, and pharmacokinetics of trastuzumab monotherapy administered on a 3-weekly schedule
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DOI：
10.1200/jco.2005.01.014
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发表时间：
2005-04-01
影响因子：
45.3
通讯作者：
Ghahramani, P
中科院分区：
文献类型：
--
作者：
Baselga, J;Carbonell, X;Ghahramani, P
目的：这项II期研究调查了曲妥珠单抗作为一线治疗人表皮生长因子受体2(HER2)阳性转移性乳腺癌(MBC)的有效性、安全性和药代动力学。患者和方法未经治疗的HER2阳性转移性乳腺癌患者接受负荷量曲妥珠单抗，8 mg/kg静脉注射(IV)，然后每隔3周静脉注射6 mg/kg曲妥珠单抗，直到疾病进展或患者停药。结果总共105例患者接受了中位数5个周期的治疗(范围1~35+)。总有效率为19%(可测量的免疫组织化学[IHC]3+和/或荧光原位杂交[FISH]阳性的患者为23%)，临床受益率(完全和部分应答加病情稳定至少6个月)为33%(可测量的中央确认的IHC 3+和/或FISH阳性的患者为36%)。中位进展时间为3.4个月(0.6至23.6个月)。与治疗相关的最常见的不良反应是发烧、发热、头痛、恶心和疲劳。基线左心室射血分数的中位数为63%；在研究过程中，这一比例没有明显变化。在这项研究中观察到的曲妥珠单抗的平均暴露与之前的每周方案研究中的相似。然而，正如预期的那样，与每周治疗相比，3周曲妥珠单抗的平均谷浓度更低，峰值更高。结论在HER2阳性的MBC患者中，按3周计划给予更高剂量的曲妥珠单抗不会影响曲妥珠单抗的疗效和安全性，平均暴露剂量与每周治疗相似。每周三次曲妥珠单抗可能是每周给药的一种方便的替代方案。(C)2005年，由美国临床肿瘤学会提供。
Purpose This phase II study investigated the efficacy, safety, and pharmacokinetics of trastuzumab monotherapy given as first-line treatment once every 3 weeks (3-weekly) in women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC).Patients and Methods Patients with previously untreated HER2-positive MBC received a loading dose of trastuzumab, 8 mg/kg intravenously (IV) and then 6 mg/kg IV at 3-week intervals until disease progression or patient withdrawal.Results In total, 105 patients received a median of five cycles of therapy (range, 1 to 35+). The overall response rate was 19% (23% in patients with measurable centrally confirmed immunohistochemistry [IHC] 3+ and/or fluorescence in situ hybridization [FISH) -positive disease) and clinical benefit rate (complete and partial responses plus stable disease for at least 6 months) was 33% (36% in patients with measurable centrally confirmed IHC 3+ and/or FISH-positive disease). Median time to progression was 3.4 months (range, 0.6 to 23.6 months). The most common treatment-related adverse events were rigors, pyrexia, headache, nausea, and fatigue. Median baseline left ventricular ejection fraction was 63%; this did not significantly change over the course of the study. The average exposure to trastuzumab observed in this study was similar to that in previous studies of the weekly regimen. However, as expected, mean trough trastuzumab concentrations were lower and peak levels were higher with 3-weekly trastuzumab compared with weekly treatments.Conclusion Administering higher doses on a 3-weekly schedule did not compromise the efficacy and safety of trastuzumab in women with HER2-positive MBC, and average exposure was similar to that observed with weekly therapy. Three-weekly trastuzumab may represent a convenient alternative to weekly administration. (c) 2005 by American Society of Clinical Oncology.