Treatment beyond progression and rechallenge with pyrotinib in HER2-positive metastatic breast cancer and brain metastases: a multicenter real-world study

Background: Despite significant advancements in treatment, patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) continue to face the challenge of drug resistance, highlighting the need to develop new drugs and treatment strategies. Pyrotinib has exhibited notable efficacy in managing HER2-positive MBC, especially in individuals with brain metastasis (BM). However, real-world evidence on the effectiveness of pyrotinib re-treatment remains limited. Objectives: This study aims to assess the efficacy of pyrotinib re-treatment—including treatment beyond progression (TBP) and rechallenge—in patients with HER2-positive MBC, particularly those with BMs, in a real-world clinical setting. Design: A retrospective, multicenter, real-world study. Methods: Patients with HER2-positive MBC who experienced progression during pyrotinib treatment and subsequently continued or resumed pyrotinib-based regimens were enrolled. Patients were divided into two groups according to the re-treatment pattern: the pyrotinib TBP group and the pyrotinib rechallenge group. The endpoints were progression-free survival (PFS) and overall survival (OS). Results: A total of 226 participants received pyrotinib TBP, whereas 33 received pyrotinib rechallenge. The median PFS of pyrotinib re-treatment (7.2 vs 6.3 months, p = 0.31) and the median OS, measured from the start of pyrotinib re-treatment (31.6 vs 21.0 months, p = 0.062), were comparable between the two groups. Among patients with BMs before pyrotinib re-treatment, the median PFS for pyrotinib re-treatment was 7.2 months, and the median OS was 25.2 months. Conclusion: Pyrotinib TBP and pyrotinib rechallenge both demonstrate potential benefits for patients with HER2-positive MBC, including those with BM.