曲妥珠单抗联合卡培他滨与拉帕替尼联合卡培他滨治疗既往曲妥珠单抗和紫杉类治疗的 HER2 阳性转移性乳腺癌患者的随机 II 期试验：WJOG6110B/ELTOP。

A randomized phase II trial of trastuzumab plus capecitabine versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and taxanes: WJOG6110B/ELTOP.

机构信息

Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan.

Department of Medical Oncology, Kindai University, Osaka, Japan.

出版信息

Breast. 2018 Aug;40:67-75. doi: 10.1016/j.breast.2018.04.010. Epub 2018 Apr 23.

DOI:10.1016/j.breast.2018.04.010

PMID:29698927

Abstract

BACKGROUND

For human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) with progression on trastuzumab-based therapy, continuing trastuzumab beyond progression and switching to lapatinib combined with chemotherapy are both valid options. We conducted an open-label, randomized phase II trial to compare the efficacy of these strategies.

PATIENTS AND METHODS

Women with HER2-positive MBC previously treated with trastuzumab and taxanes were randomly assigned to receive trastuzumab plus capecitabine (HX) or lapatinib plus capecitabine (LX). The primary endpoint was progression-free survival (PFS) and the secondary endpoints included overall survival (OS) and the objective response rate (ORR). To explore the predictive value of the differential benefit of anti-HER2 drugs, PIK3CA mutations were assessed using circulating tumor DNA.

RESULTS

Eighty-six patients (43 in each arm) were enrolled. The median PFS was 6.1 months in the HX arm and 7.1 months in the LX arm (hazard ratio, 0.81; 90% CI, 0.55-1.21; p = 0.39); the median OS was 31.0 months in the HX arm and was not reached in the LX arm (hazard ratio, 0.58; 95% CI, 0.26-1.31; p = 0.18). The ORR was 40% in the HX arm and 41% in the LX arm. PIK3CA mutations were detected in 23% of the 35 analyzed patients, and in patients without PIK3CA mutations, LX yielded relatively longer PFS and OS than HX.

CONCLUSION

In women with HER2-positive MBC previously treated with trastuzumab and taxanes, no significant differences in PFS and OS were observed between patients treated with LX and HX.

TRIAL REGISTRATION NUMBER

UMIN000005219.

摘要

背景

对于曲妥珠单抗治疗后进展的人表皮生长因子受体 2（HER2）阳性转移性乳腺癌（MBC），继续曲妥珠单抗治疗并转为拉帕替尼联合化疗，这两种方法都是有效的选择。我们进行了一项开放标签、随机的 II 期试验，以比较这两种策略的疗效。

患者和方法

先前接受过曲妥珠单抗和紫杉烷治疗的 HER2 阳性 MBC 患者被随机分配接受曲妥珠单抗加卡培他滨（HX）或拉帕替尼加卡培他滨（LX）治疗。主要终点是无进展生存期（PFS），次要终点包括总生存期（OS）和客观缓解率（ORR）。为了探索抗 HER2 药物疗效差异的预测价值，使用循环肿瘤 DNA 评估 PIK3CA 突变。

结果

共纳入 86 例患者（每组 43 例）。HX 组的中位 PFS 为 6.1 个月，LX 组为 7.1 个月（风险比，0.81；90%置信区间，0.55-1.21；p=0.39）；HX 组的中位 OS 为 31.0 个月，LX 组未达到（风险比，0.58；95%置信区间，0.26-1.31；p=0.18）。HX 组的 ORR 为 40%，LX 组为 41%。在分析的 35 例患者中，有 23%检测到 PIK3CA 突变，在没有 PIK3CA 突变的患者中，LX 组的 PFS 和 OS 相对较长。