Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan.
Department of Medical Oncology, Kindai University, Osaka, Japan.
Breast. 2018 Aug;40:67-75. doi: 10.1016/j.breast.2018.04.010. Epub 2018 Apr 23.
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.
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.
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.
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.
UMIN000005219.
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。
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。
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。
在先前接受过曲妥珠单抗和紫杉烷治疗的 HER2 阳性 MBC 患者中，LX 组与 HX 组在 PFS 和 OS 方面无显著差异。
UMIN000005219。
