Neoadjuvant Trastuzumab-rezetecan Plus Pertuzumab or Nab-Paclitaxel, Carboplatin, Trastuzumab, and Pyrotinib After Suboptimal Response to Neoadjuvant Dual HER2-Targeted Therapy Combined With Chemotherapy in HER2-Positive Early Breast Cancer: A Response-Guided Phase II Study (TAYLOR)
This prospective, response-guided phase II study investigates individualized neoadjuvant treatment strategies for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. After receiving neoadjuvant dual-HER2-targeted therapy with chemotherapy, patients are evaluated for their treatment response. Those achieving an adequate response continue the therapy, whereas patients with a suboptimal response transition to an intensified investigational regimen incorporating novel targeted agents. This adaptive approach aims to optimize pathologic response, minimize unnecessary toxicity, and explore more effective treatment options for individuals with insufficient benefit from conventional neoadjuvant therapy.
• Age ≥18 and ≤75 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Primary tumor size \>1 cm.
• Histologically confirmed invasive breast cancer, clinically staged as:
‣ Stage I (T1cN0M0)
⁃ Stage II (T1cN1M0, T2N0-1M0 or T3N0M0)
⁃ Stage III (T2N2-3M0, T3N1-3M0, or T4N0-3M0)
• HER2-positive status: IHC 3+ or IHC 2+ with positive ISH.
• Adequate major organ function:
∙ Hematology (no transfusion or hematopoietic growth factors, e.g., G-CSF, within 14 days):
⁃ Hemoglobin ≥100 g/L
• Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L
• Platelet count ≥100 × 10⁹/L
‣ Biochemistry:
⁃ Total bilirubin ≤1.5 × ULN
• ALT and AST ≤1.5 × ULN; ALP ≤2.5 × ULN
• BUN and creatinine ≤1.5 × ULN
‣ Cardiac function: LVEF ≥55% by echocardiography
• Women of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment and agree to use effective contraception during the study and for 8 weeks after the last dose.
• Voluntary written informed consent and willingness to comply with study procedures and follow-up.