{"title":"派罗替尼联合卡培他滨治疗 HER2 阳性转移性乳腺癌脑转移患者（PERMEATE 试验）：一项多中心、单臂、双队列 2 期试验的总生存期结果。","authors":"Min Yan, Quchang Ouyang, Tao Sun, Limin Niu, Jin Yang, Li Li, Yuhua Song, Chunfang Hao, Zhanhong Chen, Zhenzhen Liu, Huimin Lv, Mengwei Zhang, Liping Liu, Xiaohong Yang, Huawu Xiao, Zhichao Gao, Xiaorui Li, Fangyuan Dong, Lingxiao Zhang, Danfeng Dong, Xiuchun Chen, Jianghua Qiao, Guifang Zhang, Huiai Zeng, Jing Wang, Huihui Sun, Yajing Feng, Yuting Chen, Fangzhou Xia","doi":"10.1016/j.eclinm.2024.102837","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The phase 2 PERMEATE study has shown the antitumor activity and safety of pyrotinib plus capecitabine in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer and brain metastases. In this report, survival results were updated with extended follow-up.</p><p><strong>Methods: </strong>Between January 29, 2019 and July 10, 2020, adult patients with HER2-positive metastatic breast cancer who had radiotherapy-naïve brain metastases (cohort A, n = 59) or progressive disease after radiotherapy (cohort B, n = 19) were enrolled and received pyrotinib (400 mg once daily) and capecitabine (1000 mg/m<sup>2</sup> twice daily on days 1-14 of each 21-day cycle) until disease progression or unacceptable toxicity. Secondary endpoints progression-free survival (PFS) and overall survival (OS) were updated, and post-hoc central nervous system (CNS)-PFS was analyzed. This study is registered with ClinicalTrials.gov (NCT03691051).</p><p><strong>Findings: </strong>As of February 2, 2023, the median follow-up duration was 30.9 months (interquartile range, 16.1-39.8). Median PFS was 10.9 months (95% confidence interval [CI], 7.6-14.6) in cohort A and 5.7 months (95% CI, 3.4-11.5) in cohort B. Median OS was 35.9 months (95% CI, 24.4-not reached) in cohort A and 30.6 months (95% CI, 12.6-33.3) in cohort B. Median CNS-PFS was 13.6 months (95% CI, 9.0-15.8) in cohort A and 5.7 months (95% CI, 3.4-11.5) in cohort B. Median OS was 34.1 months (95% CI, 21.7-not reached) for 14 patients with intracranial progression only in cohort A who restarted pyrotinib plus capecitabine after local radiotherapy.</p><p><strong>Interpretation: </strong>These data support further validation in a randomized controlled trial for the assessment of pyrotinib in combination with capecitabine as systemic therapy for patients with HER2-positive breast cancer and brain metastases.</p><p><strong>Funding: </strong>National Cancer Center Climbing Foundation Key Project of China, Jiangsu Hengrui Pharmaceuticals.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":null,"pages":null},"PeriodicalIF":9.6000,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458988/pdf/","citationCount":"0","resultStr":"{\"title\":\"Pyrotinib plus capecitabine for patients with HER2-positive metastatic breast cancer and brain metastases (PERMEATE trial): overall survival results from a multicenter, single-arm, two-cohort, phase 2 trial.\",\"authors\":\"Min Yan, Quchang Ouyang, Tao Sun, Limin Niu, Jin Yang, Li Li, Yuhua Song, Chunfang Hao, Zhanhong Chen, Zhenzhen Liu, Huimin Lv, Mengwei Zhang, Liping Liu, Xiaohong Yang, Huawu Xiao, Zhichao Gao, Xiaorui Li, Fangyuan Dong, Lingxiao Zhang, Danfeng Dong, Xiuchun Chen, Jianghua Qiao, Guifang Zhang, Huiai Zeng, Jing Wang, Huihui Sun, Yajing Feng, Yuting Chen, Fangzhou Xia\",\"doi\":\"10.1016/j.eclinm.2024.102837\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The phase 2 PERMEATE study has shown the antitumor activity and safety of pyrotinib plus capecitabine in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer and brain metastases. 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引用次数: 0
摘要
研究背景PERMEATE二期研究显示，在人表皮生长因子受体2（HER2）阳性转移性乳腺癌和脑转移患者中，吡罗替尼联合卡培他滨具有抗肿瘤活性和安全性。本报告更新了延长随访后的生存结果：2019年1月29日至2020年7月10日期间，入组了HER2阳性转移性乳腺癌成年患者，这些患者有放疗无效的脑转移（队列A，n = 59）或放疗后疾病进展（队列B，n = 19），他们接受了吡罗替尼（400 mg，每天一次）和卡培他滨（1000 mg/m2，每天两次，每个21天周期的第1-14天）治疗，直到疾病进展或出现不可接受的毒性。更新了次要终点无进展生存期（PFS）和总生存期（OS），并对中枢神经系统（CNS）-PFS进行了事后分析。该研究已在 ClinicalTrials.gov (NCT03691051) 注册：截至2023年2月2日，中位随访时间为30.9个月（四分位距为16.1-39.8）。队列 A 的中位 PFS 为 10.9 个月（95% 置信区间 [CI]，7.6-14.6），队列 B 为 5.7 个月（95% CI，3.4-11.5）；队列 A 的中位 OS 为 35.9 个月（95% CI，24.4-未达到），队列 B 为 30.6 个月（95% CI，12.6-33.3）。中位OS为34.1个月（95% CI，21.7-未达到）：这些数据支持在随机对照试验中进一步验证派罗替尼联合卡培他滨作为HER2阳性乳腺癌脑转移患者全身治疗的评估结果：国家癌症中心攀登基金重点项目、江苏恒瑞医药股份有限公司。
Pyrotinib plus capecitabine for patients with HER2-positive metastatic breast cancer and brain metastases (PERMEATE trial): overall survival results from a multicenter, single-arm, two-cohort, phase 2 trial.
Background: The phase 2 PERMEATE study has shown the antitumor activity and safety of pyrotinib plus capecitabine in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer and brain metastases. In this report, survival results were updated with extended follow-up.
Methods: Between January 29, 2019 and July 10, 2020, adult patients with HER2-positive metastatic breast cancer who had radiotherapy-naïve brain metastases (cohort A, n = 59) or progressive disease after radiotherapy (cohort B, n = 19) were enrolled and received pyrotinib (400 mg once daily) and capecitabine (1000 mg/m2 twice daily on days 1-14 of each 21-day cycle) until disease progression or unacceptable toxicity. Secondary endpoints progression-free survival (PFS) and overall survival (OS) were updated, and post-hoc central nervous system (CNS)-PFS was analyzed. This study is registered with ClinicalTrials.gov (NCT03691051).
Findings: As of February 2, 2023, the median follow-up duration was 30.9 months (interquartile range, 16.1-39.8). Median PFS was 10.9 months (95% confidence interval [CI], 7.6-14.6) in cohort A and 5.7 months (95% CI, 3.4-11.5) in cohort B. Median OS was 35.9 months (95% CI, 24.4-not reached) in cohort A and 30.6 months (95% CI, 12.6-33.3) in cohort B. Median CNS-PFS was 13.6 months (95% CI, 9.0-15.8) in cohort A and 5.7 months (95% CI, 3.4-11.5) in cohort B. Median OS was 34.1 months (95% CI, 21.7-not reached) for 14 patients with intracranial progression only in cohort A who restarted pyrotinib plus capecitabine after local radiotherapy.
Interpretation: These data support further validation in a randomized controlled trial for the assessment of pyrotinib in combination with capecitabine as systemic therapy for patients with HER2-positive breast cancer and brain metastases.
Funding: National Cancer Center Climbing Foundation Key Project of China, Jiangsu Hengrui Pharmaceuticals.
期刊介绍：
eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.
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