Neoadjuvant Pyrotinib in HR-positive and HER2-low High-risk Early Breast Cancer

Neoadjuvant Pyrotinib Combined With Chemotherapy Versus Chemotherapy in HR-positive/HER2-low (IHC 2+/FISH-negative) High-risk Early Breast Cancer: an Open-lable, Multi-center, Randomized Phase III Trial

This is a multi-center, open-lable, prospective, randomized phase III clinical trial to further validate the efficacy and safety of neoadjuvant pyrotinib combined with chemotherapy in HR-positive/HER2-low (IHC 2+/FISH-negative) high-risk early breast cancer

Inclusion Criteria:

• Must participate voluntarily, sign the informed consent form, and have good compliance
• Aged ≥ 18 and ≤ 70 years old with ECOG PS score of 0-1
• Histopathological newly diagnosed, unilateral, primary invasive breast cancer
• Histopathological hormone receptor-positve ( estrogen receptor and/or progesterone receptor ≥ 10% stained cells) and HER2-low (immunochemistry 2+ with fluorescent in situ hybridization negative)
• TNM stage-IIb/III, or TNM stage-IIa with high risk (N+, G3, or MammaPrint High-risk)
• At least one evaluable target breast lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Left ventricular ejection fraction ≥ 55%, Fridericia-corrected QT interval < 450 ms in males and < 470 ms in females
• White blood cell count: ≥ 3.0 × 10^9/L, absolute neutrophil count: ≥ 1.5 × 10^9/L, platelet count: ≥ 100 × 10^9/L, hemoglobin: ≥ 90 g/L
• Aspartate aminotransferase and alanine aminotransferase: ≤ 2.5 × ULN, alkaline phosphatase: ≤ 2.5 × ULN, blood total bilirubin: ≤ 1.5 × ULN, serum creatinine: ≤ 1.5 × ULN
• Non-menopausal or non-surgically sterilized female patients identified as non-pregnant and non-lactating and consented to contraception both during the trial and within 6 months after the last administration of the test drug

Exclusion Criteria:

• Metastatic BC, bilateral BC, occult BC, inflammatory BC, or with other malignant tumors
• Known history of hypersensitivity to the study drugs
• Patients who need receive other anti-tumor treatments (except for OFS) during neoadjuvant therapy as judged by the investigators
• With severe cardiac disease or discomfort that is not expected to tolerate treatment, including but not limited to: a) arrhythmia that requires medication or is clinically significant, or high-grade atrioventricular block, b) unstable angina, myocardial infarction, heart failure or clinically significant heart valve disease, c) poorly controlled hypertension or any heart disease unsuitable for participation in this trial as determined by the investigators
• Patients who participated in a clinical trial of another drug within 4 weeks prior to randomization or underwent BC-free surgery within 4 weeks or had not fully recovered after BC-free surgery
• Other malignancy in the past 5 years, other than cured cervical carcinoma in situ, basal or squamous cell carcinoma of skin
• Patients who had basic gastrointestinal diseases (especially long-term history of diarrhea or/and constipation), inability to swallow, intestinal obstruction or other factors will affect drugs administration and absorption
• Presence of accompanying diseases that may pose serious risks to the safety of the patient or may affect the patient's ability to complete the study (including but not limited to severe diabetes mellitus, active infection, thyroid disorders, etc.) as judged by the investigator
• With a history of immunodeficiency, including acquired or congenital immunodeficiencies, or a history of organ transplantation
• Past history of confirmed neurological or mental disorders, including epilepsy or dementia
• Other conditions of the subject determined by the investigator to be unsuitable for the study