TY - JOUR
T1 - Pyrotinib plus capecitabine for patients with HER2-positive metastatic breast cancer and brain metastases (PERMEATE trial)
T2 - overall survival results from a multicenter, single-arm, two-cohort, phase 2 trial
AU - Yan, Min
AU - Ouyang, Quchang
AU - Sun, Tao
AU - Niu, Limin
AU - Yang, Jin
AU - Li, Li
AU - Song, Yuhua
AU - Hao, Chunfang
AU - Chen, Zhanhong
AU - Liu, Zhenzhen
AU - Lv, Huimin
AU - Zhang, Mengwei
AU - Liu, Liping
AU - Yang, Xiaohong
AU - Xiao, Huawu
AU - Gao, Zhichao
AU - Li, Xiaorui
AU - Dong, Fangyuan
AU - Zhang, Lingxiao
AU - Dong, Danfeng
AU - Chen, Xiuchun
AU - Qiao, Jianghua
AU - Zhang, Guifang
AU - Zeng, Huiai
AU - Wang, Jing
AU - Sun, Huihui
AU - Feng, Yajing
AU - Chen, Yuting
AU - Xia, Fangzhou
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/10
Y1 - 2024/10
N2 - 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.
AB - 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.
KW - Brain metastases
KW - Breast cancer
KW - Human epidermal growth factor receptor 2
KW - Overall survival
KW - Pyrotinib
UR - https://www.scopus.com/pages/publications/85204439194
U2 - 10.1016/j.eclinm.2024.102837
DO - 10.1016/j.eclinm.2024.102837
M3 - 文章
AN - SCOPUS:85204439194
SN - 2589-5370
VL - 76
JO - eClinicalMedicine
JF - eClinicalMedicine
M1 - 102837
ER -
