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Safety, Efficacy, and Biomarker Analysis of Pyrotinib in Combination with Capecitabine in HER2-Positive Metastatic Breast Cancer Patients: A Phase I Clinical Trial

文献类型：期刊论文

作者Li, Qiao1,2; Guan, Xiuwen1,2; Chen, Shanshan1,2; Yi, Zongbi1,2; Lan, Bo1,2; Xing, Puyuan1,2; Fan, Ying1,2; Wang, Jiayu1,2; Luo, Yang1,2; Yuan, Peng1,2
刊名CLINICAL CANCER RESEARCH
出版日期2019-09-01
卷号25期号:17页码:5212-5220
ISSN号1078-0432
DOI10.1158/1078-0432.CCR-18-4173
通讯作者Ma, Fei(drmafei@126.com) ; Xu, Binghe(xubingheBM@163.com)
英文摘要Purpose: This phase I study assessed the safety, tolerability, MTD, pharmacokinetics, antitumor activity, and predictive biomarkers of pyrotinib, an irreversible pan-ErbB inhibitor, in combination with capecitabine in patients with HER2-positive metastatic breast cancer (MBC). Patients and Methods: Patients received oral pyrotinib 160 mg, 240 mg, 320 mg, or 400 mg once daily continually plus capecitabine 1,000 mg/m(2) twice daily on days 1 to 14 of a 21-day cycle. Pharmacokinetic blood samples were collected on days 1 and 14. Next-generation sequencing was performed on circulating tumor DNA to probe for predictive biomarkers. Results: A total of 28 patients were enrolled, 22 patients were treated at the two top-level doses. Among 17 (60.7%) trastuzumab-pretreated patients, 11 received trastuzumab for metastatic disease and 6 received adjuvant trastuzumab. No dose-limited toxicity was observed. Grade 3 treatment-related adverse events (AE) occurred in 12 (42.9%) patients; anemia (14.3%) and diarrhea (10.7%) were the most common grade 3 AEs. The overall response rate (ORR) was 78.6% [95% confidence interval (CI): 59.0%-91.7%], and the clinical benefit rate was 85.7% (95% CI: 67.3%-96.0%). The median progression-free survival (PFS) was 22.1 months (95% CI: 9.0-26.2 months). ORR was 70.6% (12/17) in trastuzumab-pretreated patients and 90.9% (10/11) in trastuzumab-naive patients. Analysis of all genetic alterations in HER2-related signaling network in baseline blood samples suggested that multiple genetic alterations were significantly associated with poorer PFS compared with none or one genetic alteration (median, 16.8 vs. 29.9 months, P = 0.006). Conclusions: In a population largely naive to HER2-targeted therapy, pyrotinib in combination with capecitabine was well-tolerated and demonstrates promising antitumor activity in patients with HER2-positive MBC.
WOS关键词GROWTH-FACTOR RECEPTOR ; LAPATINIB PLUS CAPECITABINE ; TYROSINE KINASE INHIBITOR ; TRASTUZUMAB RESISTANCE ; OPEN-LABEL ; SURVIVAL ; EMTANSINE ; AMPLIFICATION ; CONTRIBUTES ; MUTATIONS
资助项目Jiangsu Hengrui Pharmaceutical CO. LTD ; National Nature Science Foundation of China[81874122] ; CAMS Initiative for Innovative Medicine[2017-12M-3-004] ; CAMS Initiative for Innovative Medicine[CAMS-12M-1-010] ; Non-profit Central Research Institute Fund of CAMS[2018PT32013] ; National Science and Technology Major Projects of the Ministry of Science and Technology of China[2015ZX09101-007]
WOS研究方向Oncology
语种英语
出版者AMER ASSOC CANCER RESEARCH
WOS记录号WOS:000484118300007
源URL[http://119.78.100.183/handle/2S10ELR8/288704]  
专题新药研究国家重点实验室
通讯作者Ma, Fei; Xu, Binghe
作者单位1.Chinese Acad Med Sci, Dept Med Oncol, Natl Canc Ctr, Natl Clin Res Ctr Canc,Canc Hosp, Beijing, Peoples R China
2.Peking Union Med Coll, Beijing 100021, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
4.Jiangsu Hengrui Med Co Ltd, Lianyungang, Jiangsu, Peoples R China
5.Chinese Acad Med Sci, State Key Lab Mol Oncol, Beijing, Peoples R China
推荐引用方式
GB/T 7714		 Li, Qiao,Guan, Xiuwen,Chen, Shanshan,et al. Safety, Efficacy, and Biomarker Analysis of Pyrotinib in Combination with Capecitabine in HER2-Positive Metastatic Breast Cancer Patients: A Phase I Clinical Trial[J]. CLINICAL CANCER RESEARCH,2019,25(17):5212-5220.
APA Li, Qiao.,Guan, Xiuwen.,Chen, Shanshan.,Yi, Zongbi.,Lan, Bo.,...&Xu, Binghe.(2019).Safety, Efficacy, and Biomarker Analysis of Pyrotinib in Combination with Capecitabine in HER2-Positive Metastatic Breast Cancer Patients: A Phase I Clinical Trial.CLINICAL CANCER RESEARCH,25(17),5212-5220.
MLA Li, Qiao,et al."Safety, Efficacy, and Biomarker Analysis of Pyrotinib in Combination with Capecitabine in HER2-Positive Metastatic Breast Cancer Patients: A Phase I Clinical Trial".CLINICAL CANCER RESEARCH 25.17(2019):5212-5220.

入库方式： OAI收割

来源：上海药物研究所

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