Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer
Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer
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DOI：
10.1200/jco.20.3.719
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发表时间：
2002-02-01
影响因子：
45.3
通讯作者：
Press, M
中科院分区：
文献类型：
--
作者：
Vogel, CL;Cobleigh, MA;Press, M
目的：评价一线单药曲妥珠单抗治疗HER2高表达转移性乳腺癌的疗效和安全性。患者和方法：114例HER2高表达转移性乳腺癌患者随机分为曲妥珠单抗4 mg/kg、每周2 mg/kg、较高8 mg/kg、每周4 mg/kg。结果：客观有效率为26%(95%可信区间[CI]，18.2%~34.4%)，完全缓解7例，部分缓解23例。免疫组织化学(IHC)法检测111例HER2过表达患者的有效率分别为35%(95%CI，24.4%~44.7%)和无有效率(95%CI，0%~15.5%)。可评估的3+和2+HER2过表达患者的临床受益率分别为48%和7%。经荧光原位杂交(FISH)分析，108例HER2基因扩增阳性和阴性患者的有效率分别为34%(95%CI，23.9%~45.7%)和7%(95%CI，0.8%~22.8%)。有客观反应的30名患者中有17名(57%)，临床受益的43名患者中有22名(51%)在12个月或以后的随访中没有疾病进展。最常见的与治疗相关的不良事件是寒战(25%的患者)、虚弱(23%)、发热(22%)、疼痛(18%)和恶心(14%)。两名患者(2%)出现心功能障碍；两人都有心脏病病史，在曲妥珠单抗停用后不需要额外干预。结论：曲妥珠单抗是有效的，耐受性良好的转移性乳腺癌患者，HER23+在IHC或FISH中过表达或基因扩增可作为一线治疗。(C)2002年，由美国临床肿瘤学会提供。
Purpose : To evaluate the efficacy and safety of first-line single-agent trastuzumab in women with HER2-overexpressing metastatic breast cancer.Patients and Methods: One hundred fourteen women with HER2-overexpressing metastatic breast cancer were randomized to receive first-line treatment with trastuzumab 4 mg/kg loading dose, followed by 2 mg/kg weekly, or a higher 8 mg/kg loading dose, followed by 4 mg/kg weekly.Results: The objective response rate was 26% (95% confidence interval [Cl], 18.2% to 34.4%), with seven complete and 23 partial responses. Response rates in 111 assessable patients with 3+ and 2+ HER2 overexpression by immunohistochemistry (IHC) were 35% (95% Cl, 24.4% to 44.7%) and none (95% Cl, 0% to 15.5%), respectively. The clinical benefit rates in assessable patients with 3+ and 2+ HER2 overexpression were 48% and 7%, respectively. The response rates in 108 assessable patients with and without HER2 gene amplification by fluorescence in situ hybridization (FISH) analysis were 34% (95% Cl, 23.9% to 45.7%) and 7% (95% Cl, 0.8% to 22.8%), respectively. Seventeen (57%) of 30 patients with an objective response and 22 (51%) of 43 patients with clinical benefit had not experienced disease progression at follow-up at 12 months or later. The most common treatment-related adverse events were chills (25% of patients), asthenia (23%), fever (22%), pain (18%), and nausea (14%). Cardiac dysfunction occurred in two patients (2%); both had histories of cardiac disease and did not require additional intervention after discontinuation of trastuzumab. There was no clear evidence of a dose-response relationship for response, survival, or adverse events.Conclusion: Single-agent trastuzumab is active and well tolerated as first-line treatment of women with metastatic breast cancer with HER2 3+ overexpression by IHC or gene amplification by FISH. (C) 2002 by American Society of Clinical Oncology.