Trastuzumab and vinorelbine as first-line therapy for HER2-overexpressing metastatic breast cancer: Multicenter phase II trial with clinical outcomes, analysis of serum tumor markers as predictive factors, and cardiac surveillance algorithm
Trastuzumab and vinorelbine as first-line therapy for HER2-overexpressing metastatic breast cancer: Multicenter phase II trial with clinical outcomes, analysis of serum tumor markers as predictive factors, and cardiac surveillance algorithm
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DOI：
10.1200/jco.2003.02.018
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发表时间：
2003-08-01
影响因子：
45.3
通讯作者：
Winer, EP
中科院分区：
文献类型：
--
作者：
Burstein, HJ;Harris, LN;Winer, EP
目的：基于曲妥珠单抗的治疗可提高人类表皮生长因子受体 2 (HER2) 阳性晚期乳腺癌女性的生存率。我们进行了一项多中心 II 期研究，以评估曲妥珠单抗联合长春瑞滨的疗效和安全性，并评估心脏监测算法和肿瘤标志物作为预后工具。 患者和方法：HER2 阳性（免疫组织化学 [IHC] 3+ 阳性或荧光原位杂交 [FISH] 阳性）转移性患者 乳腺癌接受曲妥珠单抗和长春瑞滨一线化疗以确定缓解率。资格标准是可测量的疾病和基线射血分数大于或等于 50%。对 HER2 胞外域 (ECD) 进行了系列测试。结果：来自 17 个参与中心的 54 名女性参与了该研究。总体响应率为 68%（95% 置信区间，54% 至 80%）。缓解率不受 HER2 状态测定方法 (FISH v IHC) 或既往辅助化疗的影响。治疗失败的中位时间为 5.6 个月； 38% 的患者 1 年后无进展。在维持剂量强度的情况下，并行治疗是相当可行的。患者在 90% 的预定治疗日期接受化疗和曲妥珠单抗。两名患者出现超过 1 级的心脏毒性；一名患者出现症状性心力衰竭。 16 周时筛查左心室射血分数 (LVEF) 的监测算法成功识别出有心脏毒性风险的女性。其他急性和慢性副作用是可以忍受的。第 1 周期期间 HER2 ECD 没有下降可预测肿瘤进展。结论：曲妥珠单抗和长春瑞滨构成 HER2 阳性转移性乳腺癌的有效且耐受性良好的一线治疗方法。 LVEF 正常的患者可在 16 周时通过监测 LVEF 进行观察，以识别那些有心脏毒性风险的患者。
Purpose: Trastuzumab-based therapy improves survival for women with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer. We conducted a multicenter phase II study to evaluate the efficacy and safety of trastuzumab combined with vinorelbine, and to assess cardiac surveillance algorithms and tumor markers as prognostic tools.Patients and Methods: Patients with HER2-positive (immunohistochemistry [IHC] 3+-positive or fluorescence in situ hybridization [FISH]-positive) metastatic breast cancer received first-line chemotherapy with trastuzumab and vinorelbine to determine response rate. Eligibility criteria were measurable disease and baseline ejection fraction greater than or equal to 50%. Serial testing for HER2 extracellular domain (ECD) was performed.Results: Fifty-four women from 17 participating centers were entered onto the study. The overall response rate was 68% (95% confidence interval, 54% to 80%). Response rates were not affected by method of HER2 status determination (FISH v IHC) or by prior adjuvant chemotherapy. Median time to treatment failure was 5.6 months; 38% of patients were progression free after 1 year. Concurrent therapy was quite feasible with maintained dose-intensity. Patients received both chemotherapy and trastuzumab on 90% of scheduled treatment dates. Two patients experienced cardiotoxicity in excess of grade 1; one patient experienced symptomatic heart failure. A surveillance algorithm of screening left ventricular ejection fraction (LVEF) at 16 weeks successfully identified women at risk for experiencing cardiotoxicity. Other acute and chronic side effects were tolerable. Lack of decline in HER2 ECD during cycle 1 predicted tumor progression.Conclusion: Trastuzumab and vinorelbine constitute effective and well-tolerated first-line treatment for HER2-positive metastatic breast cancer. Patients with normal LVEF can be observed with surveillance of LVEF at 16 weeks to identify those at risk for cardiotoxicity.