Neoadjuvant Study of Pyrotinib in Patients With HER2 Positive Breast Cancer

The investigators hypothesized that the experimental group (Pyrotinib+Trastuzumab+Docetaxel+ Carboplatin) could have a higher Pathological Complete Response (pCR) rate than the control group (Placebo +Trastuzumab+Docetaxel+ Carboplatin) in neoadjuvant chemotherapy.

It is proposed that 100 participants will be enrolled in this study. The target population is women with early breast cancer (stage of T1-4N0-3M0) who are eligible for primary systemic therapy.

The primary objective of the trial is to determine the pCR rate. The secondary objective of the trial is to determine the Event-free survival(EFS), Disease-free Survival (DFS), Distance Disease-free Survival (DDFS), Objective Response Rate (ORR) rate.

• Pyrotinib (Drug): Pyrotinib: 400mg orally daily
• Trastuzumab (Drug): Trastuzumab:8mg/kg iv load followed by 6mg/kg iv 3-weekly for a total of 6 cycles;
• Docetaxel (Drug): Docetaxel: 75mg/m2 for a total of 6 cycles
• Carboplatin (Drug): Carboplatin: AUC=5 for a total of 6 cycles
• Placebo Oral Tablet (Drug): Placebo Oral Tablet: 400mg orally daily

Primary outcomes

• pCR [through study completion, an average of 1 year]: Percentage of Participants With Pathological Complete Response (pCR) at the Time of Surgery.

Secondary outcomes

• EFS [Following surgery until Year 3]: Event-free survival
• DFS [Following surgery until Year 3]: Disease-free Survival
• DDFS [Following surgery until Year 3]: Distance Disease-free Survival
• ORR [Baseline up to cycle 4 (assessed at Baseline, at the time of pre-surgery)up to approximately 12 months]: Objective Response Rate

Sex: Female, ages: 18 Years to 80 Years, accepts healthy volunteers

Inclusion Criteria:

1. female patients, 18 years ≤ age ≤ 80 years；
2. Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1
3. Histologically confirmed invasive breast cancer（early stage or locally advanced）
4. HER2 positive (HER2+++ by IHC or FISH+)
5. Known hormone receptor status.
6. Cardiovascular: Baseline left ventricular ejection fraction (LVEF)≥55% measured by ECHO
7. Signed informed consent form (ICF)

Exclusion Criteria:

1. Metastatic disease (Stage IV) or inflammatory breast cancer
2. Previous or current history of malignant neoplasms, except for curatively treated: Basal and squamous cell carcinoma of the skin, Carcinoma in situ of the cervix.
3. Clinically relevant cardiovascular disease: Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled hypertension ≥180/110);
4. Unable or unwilling to swallow tablets.

• Results publication: Ding Y, Mo W, Xie X, Wang O, He X, Zhao S, Gu X, Liang C, Qin C, Ding K, Yang H, Ding X. Neoadjuvant Pyrotinib plus Trastuzumab, Docetaxel, and Carboplatin in Early or Locally Advanced Human Epidermal Receptor 2-Positive Breast Cancer in China: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial. Oncol Res Treat. 2023;46(7-8):303-311. doi: 10.1159/000531492. Epub 2023 Jun 9. PMID 37302393

• Ding Xiaowen, DR., Principal investigator, Zhejiang Cancer Hospital