Pyrotinib plus epirubicin and cyclophosphamide followed by docetaxel and trastuzumab as neoadjuvant therapy for HER2-positive early breast cancer: A multicenter non-randomized phase II study

Dual HER2 blockade combined with chemotherapy is the standard neoadjuvant approach for HER2-positive early breast cancer. Pyrotinib is an irreversible pan-HER tyrosine kinase inhibitor. This study aimed to evaluate the efficacy and safety of a pyrotinib-based neoadjuvant regimen in patients with HER2-positive early breast cancer. This multicenter, phase II prospective study evaluated neoadjuvant pyrotinib combined with epirubicin and cyclophosphamide followed by docetaxel plus trastuzumab (ACPy-THPy). A concurrent prospective cohort receiving standard docetaxel, carboplatin, trastuzumab, and pertuzumab (TCbHP) served as a real-world comparator. Propensity score matching (PSM) was applied to reduce baseline imbalances. The primary endpoint was pathological complete response (pCR). A total of 249 patients were included (ACPy-THPy, n = 120; TCbHP, n = 129). After 1:1 PSM (n = 83 per group), baseline characteristics were well balanced between groups. Before PSM, the pCR rate was numerically higher with ACPy-THPy than with TCbHP (65.0% vs. 55.0%, P = 0.109), with a significantly higher proportion of Miller-Payne grade 5 responses (70.8% vs. 58.9%, P = 0.003). After PSM, pCR rates remained numerically higher with ACPy-THPy (63.9% vs. 56.6%, P = 0.341), while Miller-Payne grade 5 responses were significantly more frequent (69.9% vs. 57.8%, P = 0.011). Objective response rates were comparable before (88.3% vs. 89.9%) and after matching (88.0% vs. 90.4%). With a median follow-up of 35.5 months, 2- and 3-year invasive disease-free survival rates were 97.3% and 95.2% in the ACPy-THPy group, compared with 94.4% and 92.5% in the TCbHP group. Diarrhea was more frequent with ACPy-THPy, with grade ≥3 events reported in 17.5%, but was clinically manageable. ACPy-THPy demonstrated promising pathological response rates and manageable toxicity in patients with HER2-positive early breast cancer. These findings support the feasibility of this pyrotinib-based neoadjuvant strategy and warrant further evaluation in randomized studies. The trial was prospectively registered with ClinicalTrials.gov (NCT04290793) on March 2, 2020.