一项口服长春瑞滨、卡培他滨和曲妥珠单抗三联疗法作为 HER2 阳性转移性乳腺癌一线治疗的 II 期研究。

Phase II study of a triple combination of oral vinorelbine, capecitabine and trastuzumab as first-line treatment in HER2-positive metastatic breast cancer.

机构信息

Mount Hospital, Curtin University, Perth, WA, Australia.

出版信息

Anticancer Res. 2013 Jun;33(6):2657-64.

Abstract

UNLABELLED

Chemotherapy plus trastuzumab is the standard first-line treatment for Human Epidermal Receptor 2-positive (HER2-positive) metastatic breast cancer. The aim of this international phase II trial was to determine the efficacy and safety profile of an oral chemotherapy doublet, oral vinorelbine plus capecitabine, and trastuzumab in this setting.

PATIENTS AND METHODS

In this single-arm, multicenter, open-label phase II study, in the first-line metastatic setting, patients received 3-weekly cycles of oral vinorelbine at 80 mg/m(2) (first cycle dose 60 mg/m(2)) day 1 and day 8, plus capecitabine at 1000 (750 if ≥ 65 years) mg/m(2) twice daily on days 1-14, plus trastuzumab at 4 mg/kg intravenously (i.v.) on day 1 (loading dose) then 2 mg/kg i.v. weekly thereafter. Treatment was continued until progression or unacceptable toxicity.

RESULTS

Fifty patients with a median age of 53.5 years were enrolled. Most (82%) had visceral involvement and 34% had more than two metastatic sites. The objective response rate (RECIST 1.0) in 44 evaluable patients was 77% [95% Confidence Interval (CI)=62-89%], including complete response in 21%. The clinical benefit rate (response or stable disease for ≥ 6 months) was 93% [95% CI=81-99%]. Median duration of response was 13.3 [95% CI=9.8-15.7] months, median progression-free survival was 12.8 [95% CI=10.8-16.9] months and median overall survival was 47.0 [95% CI=30.5-64.3] months. Median number of cycles was 10 (range 1-81). The majority of patients (72%) received more than 18 weeks and 32% more than 48 weeks of treatment. The most frequent treatment-related grade 3/4 adverse events were neutropenia (71%), hand-foot syndrome (20%) and diarrhea (16%). A low-rate of grade 2 alopecia was observed (14%).

CONCLUSION

The triple combination of oral vinorelbine, capecitabine and trastuzumab is highly active in terms of response rate, progression-free survival and overall survival, with a manageable toxicity profile.

摘要

背景

曲妥珠单抗联合化疗是治疗人表皮生长因子受体 2 阳性（HER2 阳性）转移性乳腺癌的标准一线治疗方法。本国际 II 期临床试验旨在评估口服化疗联合曲妥珠单抗治疗 HER2 阳性转移性乳腺癌的疗效和安全性。

方法

在这项单臂、多中心、开放标签的 II 期研究中，在一线转移性环境下，患者接受每周 3 次的口服长春瑞滨 80mg/m2（第 1 周期剂量 60mg/m2），第 1 天和第 8 天，同时口服卡培他滨 1000mg（65 岁以上患者为 750mg），每日 2 次，第 1-14 天；同时静脉注射曲妥珠单抗 4mg/kg（负荷剂量），第 1 天，然后每周静脉注射 2mg/kg。治疗持续到疾病进展或不可接受的毒性。

结果

50 名中位年龄为 53.5 岁的患者入组。大多数患者（82%）有内脏转移，34%有两个以上的转移灶。44 例可评估患者的客观缓解率（RECIST 1.0）为 77%[95%置信区间（CI）=62-89%]，包括 21%的完全缓解。临床获益率（缓解或疾病稳定≥6 个月）为 93%[95%CI=81-99%]。中位缓解持续时间为 13.3 个月[95%CI=9.8-15.7]，中位无进展生存期为 12.8 个月[95%CI=10.8-16.9]，中位总生存期为 47.0 个月[95%CI=30.5-64.3]。中位治疗周期数为 10 个（范围 1-81）。大多数患者（72%）接受了超过 18 周和 32%接受了超过 48 周的治疗。最常见的治疗相关 3/4 级不良事件是中性粒细胞减少症（71%）、手足综合征（20%）和腹泻（16%）。观察到脱发（14%）的发生率较低。