Final Efficacy and Safety Results of Pyrotinib Combined With Trastuzumab and Chemotherapy in Pre‐Treated Human Epidermal Growth Factor Receptor 2‐Positive Metastatic Breast Cancer

Purpose Findings from our previous study showed that the combination of pyrotinib, trastuzumab, and chemotherapy represents a viable treatment strategy with an acceptable safety profile for heavily pre‐treated human epidermal growth factor receptor 2 (HER2)‐positive metastatic breast cancer (MBC). We present here the final efficacy and safety results of our investigation. Methods Patients with HER2‐positive MBC who previously received anti‐HER2 therapies such as trastuzumab, pertuzumab, or lapatinib were treated with a combination of pyrotinib, trastuzumab, and chemotherapy. Progression‐free survival (PFS), predictive factors of PFS, and safety were updated in both the intention‐to‐treat population (ITT) and the subgroup exhibiting brain metastases (Sub‐BM). Overall survival (OS) along with its predictive factors was initially analyzed in both ITT and Sub‐BM. Results Forty patients were eligible for this analysis. After a median follow‐up of 46.6 months, 27 deaths occurred and four patients continued treatment with pyrotinib combined with trastuzumab and chemotherapy. The median PFS was 7.5 [95% confidence interval (CI), 4.5–10.5 months] and 9.1 months (95% CI, 0.0–18.9 months) in the ITT and Sub‐BM, respectively. The median OS was 32.2 (95% CI, 21.8–42.6 months) and 32.2 months (95% CI, 18.4–46.0 months) in the ITT and Sub‐BM, respectively. Cox regression analyses revealed that liver or/and lung metastases were significant adverse predictive factors for PFS ( p = 0.020) in the ITT. No new safety concerns were identified following 28 months of additional follow‐up. Adverse events were similar to those reported at the primary analyses with respect to specificity, incidence, and severity. Conclusion Updated analyses pertaining to PFS and safety were generally aligned with data obtained from initial assessments. The OS outcomes further substantiated that the combination of pyrotinib, trastuzumab, and chemotherapy is an alternative therapeutic regimen for managing HER2‐positive MBC with heavy pre‐treatment in certain situations, particularly among those with non‐visceral metastases.