Comparative efficacy and safety of anti-HER2 neoadjuvant therapy in early-stage HER2-positive breast cancer: A real-world multicenter analysis.

Abstract

e12668 Background: For patients with early-stage HER2-positive breast cancer, neoadjuvant therapy represents a cornerstone of modern management. The combination of trastuzumab and pertuzumab (HP) alongside chemotherapy constitutes the current evidence-based standard. Emerging evidence indicates that an alternative dual blockade strategy pairing trastuzumab with pyrotinib (HPy) also demonstrates promising efficacy with a manageable toxicity profile. In routine clinical practice, the selection between these two potent targeted regimens (HP versus HPy) remains a critical and unresolved decision point, necessitating further comparative evaluation. Methods: This prospective, multicenter, observational real-world study enrolled patients with stage II-III HER2-positive breast cancer. Treatment allocation to either the HP or HPy group was based on physician recommendation and patient preference. The administered chemotherapeutic backbones included: 6 cycles of TCbHP/TCbHPy, 4 cycles of EC followed by 4 cycles of THP/THPy, or 6 cycles of THP/THPy. The primary study endpoint was the total pathological complete response (tpCR) rate, defined as ypT0/is ypN0. Statistical analyses incorporated propensity score matching (PSM) to mitigate baseline imbalances. Results: Between January 2022 and June 2025, 687 patients from 10 participating hospitals were enrolled. As of the current analysis, 520 patients have completed neoadjuvant therapy and subsequent surgery with evaluable data, comprising 320 in the HP cohort and 200 in the HPy cohort. Initial comparisons revealed significant differences in chemotherapy regimens and Ki-67 expression levels between the groups. To address potential selection bias, a 1:1 PSM was performed, yielding 382 well-matched patients (191 per group) with balanced baseline characteristics. Prior to matching, the tpCR rates were 61.25% for the HP group and 53.00% for the HPy group, a difference that was not statistically significant ( P = 0.064). After PSM, the tpCR rates were 57.59% (HP) versus 53.93% (HPy), again showing no statistically significant difference ( P = 0.471). Subgroup analyses consistently demonstrated no significant interaction effects on tpCR across various patient strata (all P -interaction > 0.05). Safety analysis of the 520 patients revealed distinct toxicity profiles: the most frequent adverse event in the HPy group was diarrhea of any grade (83.0%), with a 13.5% incidence of grade ≥3 diarrhea. In contrast, the most common adverse event in the HP group was vomiting (53.6%). Conclusions: In this real-world study, the HP and HPy regimens achieved comparable pathologic complete response rates as neoadjuvant therapy for early HER2-positive breast cancer. The treatment choice can therefore be individualized based on their distinct toxicity profiles, with HPy associated more with diarrhea and HP with vomiting. Clinical trial information: ChiCTR2200056467.