Pyrotinib plus capecitabine for human epidermal growth factor receptor 2-positive metastatic breast cancer after trastuzumab and taxanes (PHENIX): a randomized, double-blind, placebo-controlled phase 3 study
Min Yan, Li Bian, Xichun Hu, Qingyuan Zhang, Quchang Ouyang, Jifeng Feng, Yongmei Yin, Tao Sun, Zhongsheng Tong, Xiaojia Wang, Herui Yao, Jianjun Zou, Xiaoyu Zhu, Zefei Jiang
Abstract
Background: Pyrotinib is an irreversible pan-ErbB inhibitor targeting epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER2), and HER4. This randomized, double-blinded phase 3 study evaluated the efficacy and safety of pyrotinib plus capecitabine for HER2-positive local relapsed or metastatic breast cancer. Methods: Patients who had been treated with trastuzumab and taxanes were randomized (2:1) to receive either oral pyrotinib or placebo (400 mg, qd) plus capecitabine (1,000 mg/m2, bid on days 1–14) for 21-day cycles, using stratified block randomization. The primary endpoint was progression-free survival (PFS) per independent review committee. Patients who progressed on placebo plus capecitabine received subsequent pyrotinib monotherapy. This study is registered with ClinicalTrials.gov (NCT02973737), enrollment is closed. Results: Between Jul 25, 2016 and Nov 27, 2017, 279 patients were randomly assigned to pyrotinib (n=185) and placebo (n=94) groups. As of May 27, 2018, median PFS was 11.1 months [95% confidence interval (CI), 9.7−16.5] vs. 4.1 months (95% CI, 2.8−4.2) in the pyrotinib vs. placebo groups, respectively [hazard ratio, 0.18 (95% CI, 0.13−0.26); P<0.001]. Seventy-one patients in the placebo group subsequently received pyrotinib, showing a response rate of 38.0% (95% CI, 26.7−49.3%) and median PFS of 5.5 months (95% CI, 4.1–6.9). The most frequent grade 3 or 4 treatment-related adverse events were diarrhea (30.8% vs. 12.8%) and hand-foot syndrome (15.7% vs. 5.3%). No treatment-related deaths were reported. Conclusions: For HER2-positive local relapsed or metastatic breast cancer after prior trastuzumab and taxanes, pyrotinib plus capecitabine yielded a statistically significant increase in PFS over placebo plus capecitabine. Pyrotinib monotherapy also showed potent anti-tumor activity.