EClinicalMedicine (Oct 2024)

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 trialResearch in context

  • 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

Journal volume & issue
Vol. 76
p. 102837

Abstract

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Summary: 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.

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