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

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

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

EClinicalMedicine. 2024 Sep 20:76:102837. doi: 10.1016/j.eclinm.2024.102837. eCollection 2024 Oct.

Authors

Min Yan¹, Quchang Ouyang², Tao Sun³, Limin Niu¹, Jin Yang⁴, Li Li⁵, Yuhua Song⁶, Chunfang Hao⁷, Zhanhong Chen⁸, Zhenzhen Liu¹, Huimin Lv¹, Mengwei Zhang¹, Liping Liu², Xiaohong Yang², Huawu Xiao², Zhichao Gao³, Xiaorui Li³, Fangyuan Dong³, Lingxiao Zhang⁴, Danfeng Dong⁴, Xiuchun Chen¹, Jianghua Qiao¹, Guifang Zhang⁹, Huiai Zeng¹, Jing Wang¹, Huihui Sun¹, Yajing Feng¹, Yuting Chen¹⁰, Fangzhou Xia¹⁰

Affiliations

¹ Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
² Department of Breast Medicine, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
³ Breast Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China.
⁴ Cancer Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
⁵ Department of Oncology, Qilu Hospital of Shandong University, Jinan, China.
⁶ Breast Cancer Center, The Affiliated Hospital of Qingdao University, Qingdao, China.
⁷ Department of Breast Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China.
⁸ Department of Breast Cancer Internal Medicine, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China.
⁹ Department of Medical Oncology, Xinxiang Central Hospital, Xinxiang, China.
¹⁰ Department of Medical Affairs, Jiangsu Hengrui Pharmaceuticals, Shanghai, China.

Abstract

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.

Keywords: Brain metastases; Breast cancer; Human epidermal growth factor receptor 2; Overall survival; Pyrotinib.

Associated data

ClinicalTrials.gov/NCT03691051