PERMEATE: Updated Results of Pyrotinib Plus Capecitabine in Patients With HER2-Positive MBC and Brain Metastases

In the phase 2 PERMEATE trial (NCT03691051), the irreversible pan-HER receptor tyrosine kinase inhibitor pyrotinib showed promising efficacy in combination with capecitabine in patients with HER2-positive metastatic breast cancer (MBC) and brain metastases; central nervous system (CNS) objective response rate (ORR) was 74.6% in the radiotherapy-naïve cohort and 42.1% in the radiotherapy-treated cohort. Updated 3-year follow-up results of this trial were presented at the 2023 ASCO annual meeting.

Eligible patients received pyrotinib (400 mg orally once daily) and capecitabine (1000 mg/m² orally twice daily on days 1-14) in 21-day cycles until disease progression or intolerable toxicity. The study allowed patients with brain-restricted progression to withdraw from study and resume study treatment after local surgery or radiotherapy until the second progression, at the discretion of the investigator. Study outcome measures included CNS ORR (per RECIST version 1.1), progression-free survival (PFS), overall survival (OS), and PFS2 (time from brain-restricted progression to second progression at any site). Data cutoff date was April 11, 2023.

At a median follow-up of 42.8 months, median PFS in the radiotherapy-naïve cohort was 10.8 months, median OS was 36.0 months, 1-year OS rate was 84.6%, and 3-year OS rate was 49.8%. A total of 14 patients in the radiotherapy-naïve cohort had brain-restricted progression and resumed study treatment following local treatment; median PFS2 in this cohort was 11.0 months. In the radiotherapy-treated cohort, median PFS was 5.6 months, median OS was 31.5 months, 1-year OS rate was 78.9%, and 3-year OS rate was 29.1%.

Dr Yan concluded “these updated results suggest that pyrotinib in combination with capecitabine can provide a long-term survival benefit for patients with HER2-positive metastatic breast cancer and brain metastases, especially for patients without prior local radiotherapy.”

Source:

Yan M, Ouyang Q, Sun T, et al. Pyrotinib plus capecitabine for patients with HER2-positive metastatic breast cancer and brain metastases: 3-year follow-up results from the phase 2 PERMEATE trial. Abstract presented at: ASCO Annual Meeting, June 2-6, 2023; Chicago, IL. Abstract 1048.