Pyrotinib-Based Therapy May Improve Survival in Patients With HER2+ Breast Cancer and Liver Metastases

Pyrotinib-based therapy demonstrated efficacy and safety in the treatment of patients with human epidermal growth factor receptor 2-positive (HER2+) advanced metastatic breast cancer (mBC) with liver metastases, according to study findings published in Frontiers in Oncology.¹

3D visualization of breast cancer cell metastasis | Image Credit: © freshidea - stock.adobe.com

HER2+ BC is one of the most common BC subtypes characterized by aggressive disease, which becomes increasingly difficult to treat. Most patients with HER2 mutations will advance to metastatic stages, and metastatic BC remains a primary determinant for mortality in BC. Distant tumors to vital organs can be difficult to treat due to metastatic heterogeneity across different organ systems that contribute to varied prognostic outcomes and therapeutic responses.¹

The liver is the third most frequent site for metastases in BC, of which the treatment landscape is particularly challenging. Untreated BC with liver metastasis has a 4- to 8-month survival period with a 5-year overall survival (OS) of approximately 8.5%, highlighting the critical need for advanced therapeutic approaches.¹

Pyrotinib is a novel tyrosine kinase inhibitor (TKI) that has shown strong anti-tumor efficacy in HER2+ mBC. After receiving conditional approval in China in 2018 for the treatment of HER2-positive metastatic or advanced disease, pyrotinib has been integrated into national clinical guidelines for the treatment of HER2+ mBC or advanced disease. The 2021 Guidelines for the Diagnosis and Treatment of Breast Cancer by the Chinese Anti-Cancer Association recommend its use in combination with capecitabine (Xeloda; Genentech) for advanced HER2+ cases. A phase 2 clinical trial further supported this approach, demonstrating that pyrotinib plus capecitabine significantly extended median progression-free survival (PFS) compared with the lapatinib (Tykerb; GSK)-capecitabine regimen.^1,2

In a retrospective cohort study, investigators assessed 91 patients with HER2-positive advanced BC who were treated with pyrotinib between March 2019 and April 2022. The participants were divided into 2 groups based on the presence (n = 29) or absence (n = 62) of liver metastases. The outcomes measured included OS, PFS, response, as well as safety.¹

The median OS was 15.8 months in patients with liver metastases, significantly shorter than the cohort without liver metastases, who had an OS of 31.4 months (P = .0036). PFS in the liver metastases group was also less favorable at a median of 8.7 months compared with 18.4 months. (P = .0272). Patients who were more likely to benefit from pyrotinib treatment were younger than 60 years of age with negative progesterone receptor expression (P = .0028), higher Ki67 expression levels (P < .0001), and absence of lymph node metastasis (P < .0001), according to a univariate analysis.¹

A comparative analysis of the data showed higher incidences of anemia in patients (58.6%) with liver metastases compared with those without (40.3%). They also reported elevated aspartate transaminase levels (31.0% vs 8.1%) in the liver metastasis group compared to the non-liver metastasis group (P < .05).¹

The findings show that pyrotinib may improve OS and PFS in patients with HER2+ mBC and liver metastases. Continued study in larger population sizes is necessary to further elucidate the agent’s role within the treatment of these patients.

REFERENCES

1. Li X, Li Y, Li T, et al. Efficacy and safety of pyrotinib in the treatment of HER2-positive liver metastatic advanced breast cancer. Front Oncol. April 8, 2025. doi: 10.3389/fonc.2025.1527277

2. Hu W, Yang J, Zhang Z, et al. Pyrotinib for HER2-positive metastatic breast cancer: a systematic review and meta-analysis. Transl Cancer Res. February 21, 2023. doi: 10.21037/tcr-22-1746