Abstract PD3-08: A randomized phase II trial of pyrotinib plus capecitabine versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer previously treated with taxanes, anthracyclines and/or trastuzumab
Authors: Xu B , Ma F , Ouyang Q , Li W , Jiang Z , Tong Z , Liu Y , Li H , Yu S , Feng J , Wang S , Hu X , Zhu X , Zou J 
Published: February 2018

Abstract
Background:Pyrotinib is an oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor (TKI) with activity against epidermal growth factor receptor (EGFR) / HER1, HER2, and HER4. Lapatinib in combination with capecitabine is one of the standards of care for patients with HER2-positive metastatic breast cancer (MBC) who have received prior taxanes, anthracyclines and/or trastuzumab.
Methods: We conducted an open label, multicenter, randomized phase II trial to comparatively evaluate efficacy and safety of pyrotinib + capecitabine (PC) or lapatinib + capecitabine (LC) in women with HER2-positive MBC. Key eligibility criteria included prior treatment with taxanes, anthracyclines and/or trastuzumab, ≤2 prior chemotherapies for metastatic disease, no CNS metastases, and no prior treatment with HER2 targeted TKI. Eligible patients were randomized 1:1 to PC Arm (P 400 mg QD D1–21 + C 1000 mg/m2BID D1–14, 21-D cycle) or LC Arm (L 1250 mg QD D1–21 + C 1000 mg/m2BID D1–14, 21-D cycle). The primary endpoint was objective response rate (ORR) as assessed by investigator, and secondary endpoints included progression-free survival (PFS), time to progression (TTP), duration of response (DoR), overall survival (OS), and safety.
Results: Between May 2015 and Mar 2016, 128 patients (65 in PC arm and 63 in LC arm) were enrolled in this study. Median age was 48 years (range 25-70), ECOG performance status was 0 (53.9%) or 1 (46.1%), 62.5% had hormone receptor-positive disease, 76.6% had visceral disease and 53.9% had received prior trastuzumab in (neo)adjuvant and/or mestastatic setting. Baseline characteristics were well balanced in two arms. Median follow-up time was 15.0 months. ORR was 78.5% in PC arm and 57.1% in LC arm (p=0.01), Median PFS was 18.1 months in PC arm and 7.0 months in LC arm (hazard ratio 0.363; 95% CI 0.228, 0.579; p&lt;0.0001), PFS benefit in PC arm compared to LC arm was observed irrespective of prior trastuzumab or not. Treatment related Grade 3-4 toxicities occurred in &gt;2% patients in PC arm vs LC arm included hand-foot syndrome (21.5% vs 19.0%), diarrhea (13.8% vs 4.8%), decreased neutrophil (7.7% vs 1.6%), decreased WBC (6.2% vs 1.6%), vomiting (4.6% vs 0%), increased AST (3.1% vs 1.6%), decreased hemoglobin (3.1% vs 1.6%), increased total bilirubin (0% vs 4.8%) and increased conjugated bilirubin (0% vs 3.2%).
Conclusions: In women with HER2-positive MBC previously treated with taxanes, anthracyclines and/or trastuzumab, pyrotinib + capecitabine yield statistically significant better PFS and ORR than lapatinib + capecitabine in this randomized phase II trial. Phase III study is ongoing to validate this finding.
Citation Format: Xu B, Ma F, Ouyang Q, Li W, Jiang Z, Tong Z, Liu Y, Li H, Yu S, Feng J, Wang S, Hu X, Zhu X, Zou J. A randomized phase II trial of pyrotinib plus capecitabine versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer previously treated with taxanes, anthracyclines and/or trastuzumab [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD3-08.