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-002)
This prospective, response-adapted phase II study evaluates the efficacy and safety of neoadjuvant culmerciclib in combination with aromatase inhibitors in patients with highly proliferative ER-positive/HER2-negative breast cancer. All patients initially receive induction treatment with culmerciclib plus endocrine therapy, followed by on-treatment assessment of biological and clinical response. Patients demonstrating an adequate response continue the same regimen, whereas those with a suboptimal response are transitioned to alternative treatment strategies prior to surgery. This adaptive approach aims to optimize treatment selection, improve therapeutic efficacy, and avoid unnecessary exposure to ineffective therapy.
⁃ Ki-67 ≥20% assessed on core needle biopsy samples. Newly diagnosed, treatment-naïve patients with stage I-IIIA disease according to the AJCC 8th edition.
⁃ Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
⁃ Adequate bone marrow function:
• Absolute neutrophil count ≥1.5 × 10⁹/L (without growth factor support within 14 days);
• Platelet count ≥100 × 10⁹/L (without transfusion or supportive therapy within 7 days);
• Hemoglobin ≥100 g/L (without transfusion within 7 days).
⁃ Adequate hepatic and renal function:
• Total bilirubin ≤1 × upper limit of normal (ULN);
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × ULN (≤5 × ULN in patients with liver metastases);
• Blood urea nitrogen and serum creatinine ≤1.5 × ULN, and creatinine clearance ≥50 mL/min (calculated using the Cockcroft-Gault formula).