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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 2018

See all articles by Fei Ma

Fei Ma

Chinese Academy of Medical Sciences - Department of Medical Oncology; Chinese Academy of Medical Sciences - Cancer Hospital; Chinese Academy of Medical Sciences - Peking Union Medical College

Quchang Ouyang

Hunan Cancer Hospital

Binghe Xu

Chinese Academy of Medical Sciences, Cancer Hospital, Department of Medical Oncology; Chinese Academy of Medical Sciences - Peking Union Medical College

Wei Li

Jilin University (JLU) - First Affiliated Hospital

Zefei Jiang

Academy of Military Medical Science

Zhongsheng Tong

Tianjin Medical University

Yunjiang Liu

Hebei Medical University

Huiping Li

Peking University - Cancer Hospital and Institute

Shiying Yu

Huazhong University of Science and Technology (Formerly Tongi Medical University)

Jifeng Feng

Jiangsu Cancer Hospital - Department of Medical Oncology; Nanjing Medical University - Jiangsu Institute of Cancer Research; Nanjing Medical University - Affiliated Cancer Hospital

Shusen Wang

Sun Yat-Sen University (SYSU) - Cancer Center

Xichun Hu

Fudan University - Shanghai Cancer Center (FUSCC)

Jianjun Zou

Jiangsu Hengrui Medicine Co., Ltd.

Xiaoyu Zhu

Jiangsu Hengrui Medicine Co., Ltd.

More...

Abstract

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

Suggested Citation

Ma, Fei and Ouyang, Quchang and Xu, Binghe and Li, Wei and Jiang, Zefei and Tong, Zhongsheng and Liu, Yunjiang and Li, Huiping and Yu, Shiying and Feng, Jifeng and Wang, Shusen and Hu, Xichun and Zou, Jianjun and Zhu, Xiaoyu, 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 (November 20, 2018). Available at SSRN: https://ssrn.com/abstract=3288216

Fei Ma

Chinese Academy of Medical Sciences - Department of Medical Oncology ( email )

Beijing
China

Chinese Academy of Medical Sciences - Cancer Hospital

China

Chinese Academy of Medical Sciences - Peking Union Medical College ( email )

NO. 9, Dongdan Santiao
Beijing, Dongcheng District
China

Quchang Ouyang

Hunan Cancer Hospital

Changsha, 410013
China

Binghe Xu (Contact Author)

Chinese Academy of Medical Sciences, Cancer Hospital, Department of Medical Oncology ( email )

China

Chinese Academy of Medical Sciences - Peking Union Medical College

NO. 9, Dongdan Santiao
Beijing, Dongcheng District
China

Wei Li

Jilin University (JLU) - First Affiliated Hospital

71 Xinmin Street
Changchun, Jilin 130021
China

Zefei Jiang

Academy of Military Medical Science

China

Zhongsheng Tong

Tianjin Medical University

Tianjin Shi
China

Yunjiang Liu

Hebei Medical University

361 East Zhongshan Road
Shijiazhuang 050017
China

Huiping Li

Peking University - Cancer Hospital and Institute

No. 38 Xueyuan Road
Haidian District
Beijing, Beijing 100871
China

Shiying Yu

Huazhong University of Science and Technology (Formerly Tongi Medical University)

1037 Luoyu Rd
Wuhan, Hubei 430074
China

Jifeng Feng

Jiangsu Cancer Hospital - Department of Medical Oncology ( email )

Nanjing
China

Nanjing Medical University - Jiangsu Institute of Cancer Research ( email )

Nanjing
China

Nanjing Medical University - Affiliated Cancer Hospital ( email )

Nanjing
China

Shusen Wang

Sun Yat-Sen University (SYSU) - Cancer Center

651 Dongfeng East Road
Guangzhou, 510060
China

Xichun Hu

Fudan University - Shanghai Cancer Center (FUSCC)

Shanghai, 200032
China

Jianjun Zou

Jiangsu Hengrui Medicine Co., Ltd.

Shanghai
China

Xiaoyu Zhu

Jiangsu Hengrui Medicine Co., Ltd.

Shanghai
China

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