Effectiveness and safety of pyrotinib-based therapy in the treatment of HER2-positive breast cancer patients with brain metastases: a multicenter real-world study

Background Approximately 30-50% of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) develop brain metastasis (BMs). Pyrotinib has shown promising efficacy in these patients. However, real-world evidence supporting its use is scarce. Therefore, we evaluate the efficacy and safety of pyrotinib-based regimens in the real world. Methods We enrolled patients with BMs from various healthcare facilities in China's Shandong region and used an updated breast-graded prognostic assessment (breast-GPA) to predict survival outcomes. Results Efficacy and toxicity were assessed in 101 patients. Overall, the median progression-free survival (PFS) was 11.0 months (95% CI, 7.6 to 14.4 months). PFS was shorter in patients with a breast-GPA of 0-2.0 (P๤0.001). Previous treatment with pertuzumab plus trastuzumab (P =0.039) and varying numbers of BMs (P = 0.028) had a significant positive correlation with PFS. Additionally, radiotherapy (P=0.033) for BMs, especially pyrotinib concurrent with radiotherapy (P=0.013), significantly prolonged the PFS. In patients with a breast-GPA of 0-2.0, a significant difference in PFS was observed depending on whether the brain was the first metastatic site (P๤0.001). Furthermore, a breast-GPA (0-2.0 vs. 2.5-4.0), and radiotherapy for BMs were found to be independent predictors of PFS. Overall, the objective response rate was 42.6%, while the disease control rate was 88.1%. Diarrhea emerged as the most common adverse event. Conclusions Pyrotinib-based therapy is effective and tolerable in HER2-positive MBC with BMs. Patients who underwent radiotherapy for BMs, particularly those who received pyrotinib concurrently with radiotherapy, exhibited a more favorable prognosis. MicroAbstract Pyrotinib is an oral drug used for patients of HER2-positive breast cancer with brain metastases. In this study, we assessed the effectiveness, safety, and prognostic factors of pyrotinib-based regimen. Patients treated with radiotherapy had a better prognosis, and pyrotinib concurrent with radiotherapy was a viable option.