Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease
Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease
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DOI：
10.1200/jco.1999.17.9.2639
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发表时间：
1999-09-01
影响因子：
45.3
通讯作者：
Slamon, DJ
中科院分区：
文献类型：
--
作者：
Cobleigh, MA;Vogel, CL;Slamon, DJ
HER 2蛋白的过度表达发生在25%至30%的人类乳腺癌中，并导致疾病的特别侵袭性形式。重组人源化抗HER 2单克隆抗体作为单一药物的疗效和安全性进行了评估，在妇女HER 2过度表达转移性乳腺癌化疗后转移diseases.Patients和方法：二百二十二名妇女，HER 2过度表达转移性乳腺癌后进展一个或两个化疗方案，被纳入。患者接受了4毫克/公斤的负荷剂量静脉注射，然后由2毫克/公斤的维持剂量在每周intervention.Results：研究患者有晚期转移性疾病，并接受了广泛的治疗。一个设盲的独立反应评估委员会确定了8例完全反应和26例部分反应，意向治疗人群的客观反应率为15%（95%置信区间，11%至21%）。中位缓解持续时间为9.1个月;中位生存期为13个月。最常见的不良事件（发生在约40%的患者中）是输注相关的发热和/或寒战，通常仅在首次输注期间发生，并且严重程度为轻度至中度，这些症状用对乙酰氨基酚和/或苯海拉明成功治疗，最具临床意义的不良事件是心功能不全，发生在4.7%的患者中，仅1%的患者因治疗相关不良事件而中止研究，结论：重组人源化抗-HER 2单克隆抗体，作为单一药剂施用，产生持久的客观应答，并且在患有HER-过表达转移性乳腺癌且在转移性疾病化疗后进展的女性中耐受良好，化疗常见的副作用，如脱发、粘膜炎和中性粒细胞减少症，很少见到。(C)1999年，美国临床肿瘤学会。
Purpose: Overexpression of the HER2 protein occurs in 25% to 30% of human breast cancers and leads to a particularly aggressive form of the disease. Efficacy and safety of recombinant humanized anti-HER2 monoclonal antibody as a single agent was evaluated in women with HER2-overexpressing metastatic breast cancer that had progressed after chemotherapy for metastatic disease.Patients and Methods: Two hundred twenty-two women, with HER2-overexpressing metastatic breast cancer that had progressed after one or two chemotherapy regimens, were enrolled. Patients received a loading dose of 4 mg/kg intravenously, followed by a 2-mg/kg maintenance dose at weekly intervals.Results: Study patients had advanced metastatic disease and had received extensive prior therapy. A blinded, independent response evaluation committee identified eight complete and 26 partial responses, for an objective response rate of 15% in the intent-to-treat population (95% confidence interval, 11% to 21%). The median duration of response wets 9.1 months; the median duration of survival was 13 months. The most common adverse events, which occurred in approximately 40% of patients, were infusion-associated fever and/or chills that usually occurred only during the first infusion, and were of mild to moderate severity, These symptoms were treated successfully with acetaminophen and/or diphenhydramine, The most clinically significant adverse event was cardiac dysfunction, which occurred in 4.7% of patients, Only 1% of patients discontinued the study because of treatment-related adverse events,Conclusion: Recombinant humanized anti-HER2 monoclonal antibody, administered as a single agent, produces durable objective responses and is well tolerated by women with HERS-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease, Side effects that are commonly observed with chemotherapy, such as alopecia, mucositis, and neutropenia, are rarely seen. (C) 1999 by American Society of Clinical Oncology.