Pyrotinib Plus Trastuzumab and Chemotherapy for HER2-Positive Early Breast Cancer

Efficacy and Safety of Pyrotinib and Trastuzumab Combined With Pegylated Liposomal Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel for Injection Albumin Bound as Neoadjuvant Therapy for Early HER2-Positive Breast Cancer

This is a single-arm, multicenter clinical study designed to evaluate the efficacy and safety of pyrotinib and trastuzumab combined with pegylated liposomal doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel for injection albumin bound as neoadjuvant therapy in patients with early HER2-positive breast cancer.

Eligible patients will receive 8 cycles of neoadjuvant treatment. Pyrotinib will be administered orally once daily, and trastuzumab will be administered intravenously every 3 weeks. During the first 4 cycles, patients will receive pegylated liposomal doxorubicin hydrochloride and cyclophosphamide. During the subsequent 4 cycles, patients will receive paclitaxel for injection albumin bound. The primary outcome is total pathological complete response rate. Secondary outcomes include breast pathological complete response rate, lymph node pathological complete response rate, objective response rate, event-free survival, distant disease-free survival, overall survival, and safety.

Inclusion Criteria:

• Female patients aged 18 to 65 years.
• Patients with previously untreated invasive breast cancer confirmed by pathological examination.
• HER2-positive breast cancer, defined as immunohistochemistry (IHC) 3+ or IHC 2+ with HER2 gene amplification confirmed by in situ hybridization (ISH), regardless of hormone receptor status.
• Clinical stage T2N0-3M0 or any T/N1-N3M0 according to the 8th edition of the American Joint Committee on Cancer (AJCC) staging system.
• At least one measurable lesion according to RECIST version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function, meeting all of the following criteria:
• Hemoglobin ≥100 g/L.
• Absolute neutrophil count ≥1.5 × 10^9/L.
• Platelet count ≥100 × 10^9/L.
• Total bilirubin ≤1 × upper limit of normal (ULN).
• Alanine aminotransferase and aspartate aminotransferase ≤1.5 × ULN.
• Alkaline phosphatase ≤2.5 × ULN.
• Blood urea nitrogen and serum creatinine ≤1.5 × ULN.
• Left ventricular ejection fraction ≥55% by echocardiography.
• Women of childbearing potential must have a negative serum pregnancy test within 7 days before enrollment and agree to use appropriate contraception during the study and for 8 weeks after the last dose of study treatment.
• Patients must voluntarily participate in the study, sign the informed consent form, have good compliance, and be willing to cooperate with follow-up.

Exclusion Criteria:

• Prior receipt of any anti-tumor therapy, including chemotherapy, radiotherapy, molecular targeted therapy, or endocrine therapy.
• Concurrent receipt of any other anti-tumor therapy.
• Bilateral breast cancer, inflammatory breast cancer, or occult breast cancer.
• Stage IV breast cancer.
• Breast cancer not confirmed by pathological examination.
• History of other malignancies within 5 years, except cured carcinoma in situ of the cervix.
• Severe dysfunction of major organs, including the heart, liver, or kidney.
• Inability to swallow, chronic diarrhea, intestinal obstruction, or other factors that may affect drug administration or absorption.
• Participation in another drug clinical trial within 4 weeks before enrollment.
• Known history of allergy to any component of the study treatment.
• History of immunodeficiency, including positive HIV test, hepatitis C virus infection, active hepatitis B virus infection, other acquired or congenital immunodeficiency diseases, or history of organ transplantation.
• History of any cardiac disease, including clinically significant arrhythmia requiring medication, myocardial infarction, heart failure, or any other cardiac disease judged by the investigator to make the patient unsuitable for this study.
• Pregnant or breastfeeding women, women of childbearing potential with a positive baseline pregnancy test, or women of childbearing potential unwilling to use effective contraception throughout the study.
• Serious concomitant diseases that, in the investigator's judgment, may compromise patient safety or affect completion of the study, including but not limited to uncontrolled severe hypertension, severe diabetes mellitus, or active infection.
• Clear history of neurological or psychiatric disorders, including epilepsy or dementia.
• Any other condition that, in the investigator's opinion, makes the patient unsuitable for participation in this study.