Preclinical study and phase 2 trial of neoadjuvant pyrotinib combined with chemotherapy in luminal/HER2-low breast cancer: PILHLE-001 study.

IF 11.7 1区医学 Q1 CELL BIOLOGY Cell Reports Medicine Pub Date : 2024-11-02 DOI:10.1016/j.xcrm.2024.101807

Chang Gong, Yuan Xia, Yingying Zhu, Yaping Yang, Qun Lin, Qiang Liu, Wenqian Yang, Li Ling, Jiajie Zhong, Zhuxi Duan, Yunjie Zeng, Ziliang Cheng, Jun Shen, Yinduo Zeng, Louis Wing Cheong Chow, Erwei Song

{"title":"Preclinical study and phase 2 trial of neoadjuvant pyrotinib combined with chemotherapy in luminal/HER2-low breast cancer: PILHLE-001 study.","authors":"Chang Gong, Yuan Xia, Yingying Zhu, Yaping Yang, Qun Lin, Qiang Liu, Wenqian Yang, Li Ling, Jiajie Zhong, Zhuxi Duan, Yunjie Zeng, Ziliang Cheng, Jun Shen, Yinduo Zeng, Louis Wing Cheong Chow, Erwei Song","doi":"10.1016/j.xcrm.2024.101807","DOIUrl":null,"url":null,"abstract":"<p><p>The prognosis of patients with luminal/human epidermal growth factor receptor 2 (HER2)-low early breast cancer (EBC) needs to be improved. This preclinical study and phase 2 trial (ChiCTR2100047233) aims to explore the efficacy and safety of pyrotinib (a pan-HER tyrosine kinase inhibitor) plus chemotherapy in this population. Our preclinical experiments indicate a synergistic anti-tumor effect of pyrotinib plus chemotherapy in luminal/HER2-low (immunochemistry [IHC] 2+/fluorescent in situ hybridization [FISH]-negative) breast cancer models. Furthermore, 48 women with luminal/HER2-low (IHC 2+/FISH-negative) high-risk EBC are enrolled to receive neoadjuvant pyrotinib plus chemotherapy (epirubicin-cyclophosphamide followed by docetaxel). Ultimately, 26 (54.2%; 95% confidence interval [CI] 39.2%-68.6%) patients achieve the primary endpoint (residual cancer burden [RCB] 0/I). Treatment-related adverse events of grade ≥3 occur in 21 (43.8%) patients, with the most prevalent being diarrhea (10 [20.8%]). In conclusion, neoadjuvant pyrotinib plus chemotherapy has encouraging efficacy and manageable toxicity in women with luminal/HER2-low (IHC 2+/FISH-negative) high-risk EBC. This regimen warrants to be further validated.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7000,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Reports Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.xcrm.2024.101807","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The prognosis of patients with luminal/human epidermal growth factor receptor 2 (HER2)-low early breast cancer (EBC) needs to be improved. This preclinical study and phase 2 trial (ChiCTR2100047233) aims to explore the efficacy and safety of pyrotinib (a pan-HER tyrosine kinase inhibitor) plus chemotherapy in this population. Our preclinical experiments indicate a synergistic anti-tumor effect of pyrotinib plus chemotherapy in luminal/HER2-low (immunochemistry [IHC] 2+/fluorescent in situ hybridization [FISH]-negative) breast cancer models. Furthermore, 48 women with luminal/HER2-low (IHC 2+/FISH-negative) high-risk EBC are enrolled to receive neoadjuvant pyrotinib plus chemotherapy (epirubicin-cyclophosphamide followed by docetaxel). Ultimately, 26 (54.2%; 95% confidence interval [CI] 39.2%-68.6%) patients achieve the primary endpoint (residual cancer burden [RCB] 0/I). Treatment-related adverse events of grade ≥3 occur in 21 (43.8%) patients, with the most prevalent being diarrhea (10 [20.8%]). In conclusion, neoadjuvant pyrotinib plus chemotherapy has encouraging efficacy and manageable toxicity in women with luminal/HER2-low (IHC 2+/FISH-negative) high-risk EBC. This regimen warrants to be further validated.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

新辅助治疗派罗替尼联合化疗治疗腔隙性/HER2低下乳腺癌的临床前研究和2期试验：PILHLE-001研究。

腔隙性/人表皮生长因子受体2（HER2）-低度早期乳腺癌（EBC）患者的预后亟待改善。这项临床前研究和二期试验（ChiCTR2100047233）旨在探索派罗替尼（一种泛HER酪氨酸激酶抑制剂）联合化疗在这一人群中的疗效和安全性。我们的临床前实验表明，在管腔/HER2低（免疫化学[IHC] 2+/荧光原位杂交[FISH]阴性）乳腺癌模型中，派罗替尼联合化疗具有协同抗肿瘤作用。此外，48名患有管腔/HER2-低（免疫化学[IHC] 2+/荧光原位杂交[FISH]阴性）高危EBC的妇女入组，接受新辅助派罗替尼加化疗（表柔比星-环磷酰胺，然后是多西他赛）。最终，26 例（54.2%；95% 置信区间 [CI] 39.2%-68.6%）患者达到主要终点（残留癌负担 [RCB] 0/I）。21例（43.8%）患者发生了≥3级的治疗相关不良事件，其中最常见的是腹泻（10例[20.8%]）。总之，对于管腔/HER2低（IHC 2+/FISH阴性）高危EBC女性患者，新辅助治疗派罗替尼加化疗具有令人鼓舞的疗效和可控的毒性。该方案有待进一步验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.