Pyrotinib or Lapatinib Combined with Capecitabine in Women with HER2-Positive Metastatic Breast Cancer Previously Treated with Taxanes, Anthracyclines, And/Or Trastuzumab: An Open-Label, Randomised, Phase 2 Study
111 Pages Posted: 22 Nov 2018More...
Background: Pyrotinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor, showed promising antitumour activity and acceptable tolerability in a phase 1 breast cancer trial. We assessed the efficacy and tolerability of pyrotinib versus lapatinib, both with capecitabine, in women with HER2-positive metastatic breast cancer.
Methods: This open-label, multicentre, randomised phase 2 study was conducted at 11 hospitals in China in patients with HER2-positive relapsed or metastatic breast cancer previously treated with taxanes, anthracyclines and/or trastuzumab, and two or fewer chemotherapy regimens. Using stratified block randomisation, patients were assigned (1:1) to receive either 400 mg pyrotinib or 1250 mg lapatinib orally once daily for 21-day cycles in combination with capecitabine (1000 mg/m2 orally twice daily on days 1-14). The primary endpoint (investigator-assessed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1) and safety were assessed in patients who received ≥1 dose of study treatment.
Findings: Between May 29, 2015 and March 15, 2016, 128 eligible patients were randomly assigned to the pyrotinib (n=65) or lapatinib (n=63) treatment groups. The objective response rate was 78·5% (95% CI 68·5-88·5) with pyrotinib and 57·1% (95% CI 44·9-69·4) with lapatinib (treatment difference 21·3%, 95% CI 4·0-38·7; p=0·01). The most frequent grade 3-4 adverse events were hand-foot syndrome in 16 (24·6%) of 65 patients in the pyrotinib group vs 13 (20·6%) of 63 in the lapatinib group; diarrhoea (ten [15·4%] vs three [4·8%]); and decreased neutrophil count (six [9·2%] vs two [3·2%]).
Interpretation: These findings support the use of pyrotinib plus capecitabine as an effective treatment option for pre-treated relapsed or metastatic breast cancer.
Clinical Trial Number: This trial is registered with ClinicalTrials.gov (NCT02422199) and is closed to new participants
Funding Statement: Jiangsu Hengrui Medicine Co., Ltd., CAMS Initiative for Innovative Medicine (CAMS-12M-1-010) and Grant No. 2015ZX09101007003 from National Science and Technology Major.
Declaration of Interests: JZ and XZ are employed by Jiangsu Hengrui Medicine Co., Ltd. All other authors report no potential conflicts.
Ethics Approval Statement: If a patient agreed to participate, she was required to provide written informed consent before enrollment. Investigations were performed in accordance with Chinese laws and regulations and the Helsinki declaration, after approval by the local ethics committee at each participating site.
Keywords: Pyrotinib, lapatinib, HER2-positive metastatic breast cancer
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