Comparable clinical efficacy of pyrotinib in trastuzumab-naive and trastuzumab-exposed HER2-positive advanced breast cancer patients: A prospective, multicenter, real-world study.

Abstract

e13025 Background: Pyrotinib is an irreversible pan-HER tyrosine kinase inhibitor that has shown significant efficacy in HER2-positive breast cancer. However, in real-world clinical practice, the effectiveness of first-line pyrotinib-based regimens has not been well characterized. This study supplemented the corresponding evidence. Methods: This is a prospective observational study conducted at three centers in China. Patients with HER2-positive advanced breast cancer who planned to receive first-line pyrotinib-based therapy were enrolled. Treatment regimen and the dose of pyrotinib were determined by treating physicians according to routine clinical practice. The primary outcome was real-world progression-free survival (rwPFS). Results: From May 2024 to November 2025, 156 patients were enrolled, with 152 having available baseline characteristics. The majority of patients had trastuzumab-naïve (48.0% [73/152]), trastuzumab-sensitive (disease recurrence more than 12 months after completion of adjuvant trastuzumab therapy 45.4% [69/152]), trastuzumab-resistance (disease progression while on trastuzumab therapy, or relapse/metastasis occurring within 12 months of trastuzumab discontinuation in the (neo)adjuvant phase,.6.6% [10/152]) disease, and had visceral metastases (55.9% [85/152]). As of November 30, 2025, a total of 108 patients had completed tumor response assessments.The real-world objective response rate was 53.7% (58/108), 61.2% (30/49) in the trastuzumab-naïve subgroup and 52.0% (26/50) in the trastuzumab-sensitive subgroup. The estimated 12-month and 18-month rwPFS rates were 81.1% (95% CI: 71.1–92.6) and 65.2% (95% CI: 49.0–86.8) for all the 156 patients, 78.0% (95% CI: 63.1–96.5) and 65.0% (95% CI: 42.9–98.6) for patients with trastuzumab-naïve disease (n = 73), and 89.5% (95% CI: 78.5–100) and 70.5% (95% CI: 49.3–100) for trastuzumab-sensitive patients (n = 69), respectively. The most common grade 3 adverse events (AEs) included alopecia (28.8% [45/156]), diarrhea (20.5% [32/156]), and decreased neutrophil count (9.6% [15/156]). No grade ≥4 AEs were reported. Conclusions: First-line pyrotinib-based regimens showed favorable effectiveness and manageable safety profiles for patients with HER2-positive advanced breast cancer in the real-world setting, including those with trastuzumab-naïve and trastuzumab-sensitive disease. These findings support their use in routine clinical practice. Clinical trial information: NCT06495541 .