Comparative efficacy and safety of Zercepac® plus pyrotinib versus Zercepac® plus pertuzumab in combination with chemotherapy as neoadjuvant therapy for HER2-positive breast cancer: A retrospective study

Introduction: HER2-positive breast cancer needs better neoadjuvant options. Pyrotinib (Py) with trastuzumab biosimilar may offer an alternative to dual blockade. Objective: This study analyzed the short-term efficacy and safety of Zercepac®, a trastuzumab biosimilar, combined with either Py or pertuzumab and chemotherapy in neoadjuvant therapy for HER2-positive breast cancer. It also compared the efficacy and safety of Zercepac®-pyrotinib-chemotherapy versus Zercepac®-pertuzumab-chemotherapy regimens. Methods: Clinical data from 62 HER2-positive breast cancer patients who underwent neoadjuvant therapy with Zercepac® combined with Py or pertuzumab and chemotherapy at Anhui Cancer Hospital (February 2021 to December 2023) were retrospectively analyzed. Efficacy and safety were compared among TCbHP (29 cases), TCbHPy (8 cases), THP (9 cases), and TCbH (16 cases) groups. Statistical methods were used to identify factors influencing total pathological complete response (tpCR). Results: Among the 62 patients, 45 (72.6%) had invasive breast cancer, 11 (17.7%) had invasive carcinomas with intraductal components, five (8.1%) had invasive carcinomas with ductal carcinoma in situ, and one (1.6%) had invasive carcinoma with mucinous features. Age and advanced clinical stage were independent risk factors for tpCR (p<0.001). The TCbHPy group showed comparable efficacy to TCbHP (p=0.25). Alopecia (91.9%) was the most common adverse event. Diarrhea incidence was significantly higher in TCbHPy than in TCbHP (p<0.001); however, no grade 4 diarrhea occurred, and triple antidiarrheal therapy reduced its severity to grade 1. Conclusion: Zercepac® is effective and safe in neoadjuvant therapy for HER2-positive breast cancer. Py (≥400 mg) may improve tpCR rates, with diarrhea as the main adverse effect. TCbHPy regimen demonstrated non-inferior efficacy to TCbHP.