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

作者：Takano Toshimi^*; Tsurutani Junji; Takahashi Masato; Yamanaka Takeharu; Sakai Kazuko; Ito Yoshinori; Fukuoka Junya; Kimura Hideharu; Kawabata Hidetaka; Tamura Kenji; Matsumoto Koji; Aogi Kenjiro; Sato Kazuhiko; Nishio Kazuto; Nakagawa Kazuhiko; Saeki Toshiaki

来源：Breast, 2018, 40: 67-75.

DOI：10.1016/j.breast.2018.04.010

• Lapatinib
• Trastuzumab
• Beyond progression
• PIK3CA
• Brain metastasis
• Circulating tumor DNA

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.

• 出版日期2018-8
• 单位中国医学科学院肿瘤医院