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Life sciences · Journal article
Frontiers in Pharmacology · October 15, 2026
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Background Direct comparative evidence between taxane plus trastuzumab plus pyrotinib (THPyro) and taxane plus trastuzumab plus pertuzumab (THP) as first-line therapy for HER2-positive advanced breast cancer remains limited. Methods This multicenter retrospective real-world cohort study included 181 female patients in Xinjiang, China who initiated first-line THP or THPyro between 1 January 2020 and 30 September 2025. Propensity score matching generated 60 matched pairs. The primary endpoint was progression-free survival (PFS). Median follow-up in the matched cohort was 28.4 months. Results After matching, baseline characteristics were well balanced. THPyro showed numerically longer median PFS than THP (20.1 vs. 17.6 months; log-rank P = 0.086), and the stratified Cox model showed a non-significant trend toward reduced progression risk (hazard ratio, 0.478; 95% confidence interval, 0.216–1.061). Restricted mean survival time (RMST) analysis demonstrated a significant 24-month PFS gain with THPyro (absolute difference, 2.41 months; P = 0.007). Objective response and disease control rates were comparable. Brain metastasis status was the most prominent potential effect modifier, with an exploratory signal observed in patients with baseline brain metastases. THPyro was associated with more diarrhea, and higher albumin level and prophylactic loperamide use were associated with a lower observed risk of grade ≥2 diarrhea. Conclusion First-line THPyro was associated with a non-significant trend toward longer PFS and a significant 24-month RMST gain compared with THP in this retrospective matched cohort. An exploratory signal was observed among patients with baseline brain metastases, while diarrhea was more frequent and required proactive management.