This study evaluates HER2-PET/CT-guided dynamic optimization of neoadjuvant therapy in patients with early-stage HER2-positive breast cancer. Based on metabolic response after two cycles, patients receive either intenstified treatment (Arm A) or de-escalation treatment (Arm B), alongside with a concurrent standard-treatment control group (Arm C). The study aims to establish a response-adaptive, imaging-guided treatment paradigm to optimize neoadjuvant therapy in HER2-positive breast cancer.
This is a prospective, two-arm, interventional study. Eligible patients with early-stage HER2-positive breast cancer are enrolled into Arm A (TCbHP: trastuzumab, pertuzumab, docetaxel/nab-paclitaxel, and carboplatin) or Arm B (trastuzumab, pertuzumab, CDK4/6 inhibitor, and aromatase inhibitor), based on molecular subtype and patient preference. Patients in the control group (ArmC) will receive standard TCbHP therapy without intervention. All patients will undergo HER2-PET/CT imaging at baseline and after two cycles of treatment. Metabolic response, defined as a ≥40% reduction in SUVmax of target lesions, guides subsequent therapy: responders continue the initial regimen, while non-responders switch to an alternative strategy (ADC in Arm A or TCbHP in Arm B). The primary endpoint is the total pathological complete response (tpCR) rate in Arm A and ArmB.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
156
8 mg/kg first dose, followed 6 mg/kg given into the vein (IV; intravenously) every 21 days
840 mg first dose, followed 420 mg given by IV every 21 days
600 mg Pertuzumab, 600 mg Trastuzumab, and 20,000 units hyaluronidase will be given by subcutaneous injection every 21 days
Docetaxe 75mg/m²/ Nab-paclitaxel:260mg/m²
AUC6
Ribociclib 600mg once daily every 21days/ Dalpiciclib 150mg once daily every 21days/ Palbociclib 125mg once daily every 21days
Letrozole 2.5mg once daily/ Anastrozole 1mg once daily/ Exemestane25mg once daily
T-Dxd: 5.4mg/kg given into the vein (IV; intravenously) every 21 days SHR-A1811: 4.8mg/kg given into the vein (IV; intravenously) every 21 days
rate of pathologic complete response (pCR)
Proportion of participants who have no evidence by H\&E staining of residual invasive disease
Time frame: Up to 6 months after treatment start
SUVmax change on HER2-PET
The change in SUVmax value of HER2-PET after 2 cycles of treatment compared to the baseline level
Time frame: Up to 6 months after treatment start
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