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Triple HER2 Blockade With Trastuzumab, Pertuzumab, and Pyrotinib Versus Dual HER2 Blockade in the Neoadjuvant Treatment of HER2‐Positive Breast Cancer: A Randomized, Phase II Study

2026/01/18 by Jiahui Huang, Haoyu Wang, Yiwei Tong +15 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Breast Cancer Treatment Studies #Cancer Treatment and Pharmacology #HER2/EGFR in Cancer Research

paper · pdf · doi:10.1002/mco2.70611

openalex publication_date 2026/01/18 · openalex created_date 2026/01/20 · openalex updated_date 2026/05/21

Abstract

ABSTRACT This study aimed to evaluate the efficacy and safety of triple human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab, pertuzumab, and pyrotinib (TPPy) versus dual HER2 blockade with trastuzumab and pertuzumab (TP) in the neoadjuvant treatment of HER2‐positive breast cancer. Patients with stage II–III HER2‐positive breast cancer were randomized (1:1) to receive TPPy or TP alongside weekly nab‐paclitaxel for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/isN0). Exploratory biomarker and pathway analysis was done to identify patients benefiting from pyrotinib. A total of 109 patients were enrolled, and 108 received treatment: 55 in the TPPy group and 53 in the TP group. The tpCR rate was 65.5% (95% confidence interval [CI]: 51.4%–77.8%) in the TPPy group, and 60.4% (95% CI: 46.0%–73.5%) in the TP group ( p = 0.585). In the TPPy group, 52 (94.5%) and 23 (41.8%) patients experienced dose interruption and discontinuation, respectively. The most common grade ≥3 adverse events in the TPPy and TP groups were diarrhea (58.1% vs. 0%) and neutropenia (23.6% vs. 15.1%). In conclusion, triple HER2 blockade did not improve tpCR rates compared with dual blockade but was associated with greater toxicity, particularly diarrhea.

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