Neoadjuvant Pyrotinib-to-pertuzumab in HER2+ eBC

Neoadjuvant Pyrotinib, Trastuzumab, Docetaxel Followed by Pertuzumab, Trastuzumab, Docetaxel Versus Pertuzumab, Trastuzumab, Docetaxel for the Treatment of Early or Locally Advanced HER2-Positive Breast Cancer: A Randomized, Multicenter, Open-Label Study

This is a randomized, open-label, superiority, multicenter clinical trial for patients with early or locally advanced (T≥2cm, N0-3, M0) HER2-positive breast cancer. It aims to compare the efficacy of neoadjuvant treatment with 2 cycles of Pyrotinib + Trastuzumab + Docetaxel followed by 2 cycles of Pertuzumab + Trastuzumab + Docetaxel versus 4 cycles of Pertuzumab + Trastuzumab + Docetaxel. Exploratory analyses of ctDNA clearance rate and MRI response will also be conducted.

Inclusion Criteria:

1. Signed informed consent.

2. Age: Female patients aged 18-70 years.

3. Breast cancer meeting the following criteria:

   1. Histologically confirmed invasive breast cancer, with primary tumor diameter ≥ 2.0 cm, Stage II-III as assessed by local standard methods.
   2. HER2-positive breast cancer, defined as Immunohistochemistry (IHC) score 3+ or In Situ Hybridization (ISH) showing HER2 gene amplification.

4. Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 1.

5. All required baseline laboratory tests and imaging studies completed before randomization.

6. Adequate organ function

7. For non-menopausal (amenorrhea < 12 months) or non-surgically sterile female patients (without ovaries and/or uterus): Agreement to abstain or use reliable and effective contraception during treatment and for at least 6 months after the last dose of study treatment.

8. Investigator judgment that the patient can comply with the study protocol.

Exclusion Criteria:

1. Bilateral breast cancer or metastatic (Stage IV) breast cancer.

2. Significant cardiac disease:

   1. History of myocardial infarction, acute coronary syndrome, or coronary angioplasty/stenting/bypass within the past 6 months.
   2. New York Heart Association (NYHA) Class II-IV congestive heart failure (CHF) or history of NYHA Class III or IV CHF.
   3. High-risk uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate > 100 bpm, significant ventricular arrhythmias (e.g., ventricular tachycardia), or higher-grade atrioventricular (AV) block.
   4. Angina requiring anti-anginal medication.
   5. Clinically significant valvular heart disease.
   6. ECG evidence of transmural myocardial infarction.

3. Other malignancies within the past 5 years, except cured carcinoma in situ of the cervix or non-melanoma skin cancer.

4. Severe systemic infection or patients with other serious diseases.

5. Major non-breast surgery within 4 weeks of randomization, or patients who have not fully recovered from such surgery.

6. Known history of Human Immunodeficiency Virus (HIV) infection.

7. Active hepatitis B or hepatitis C virus infection.

8. Known allergy or intolerance to the study drugs or their excipients.

9. Prior cytotoxic chemotherapy, endocrine therapy, biological therapy, or radiotherapy for any reason.

10. Currently enrolled in or previously participated in a study of an investigational drug and received investigational treatment or used an investigational device within 4 weeks before the first dose of study treatment (12 months for investigational drugs/devices with anti-cancer or anti-proliferative properties).

11. Vaccination with a live vaccine within 30 days before the first dose of the investigational drug.

12. Psychiatric illness or substance abuse history that could affect compliance with trial requirements.

13. Pregnancy or breastfeeding, or female patients of childbearing potential who refuse to take appropriate contraceptive measures during the trial.

14. Patients judged by the investigator to be unsuitable for participation in this study.