This study is a response-adapted, multicenter, interventional trial enrolling patients with HER2-positive early or locally advanced breast cancer. All enrolled patients will first receive 2 cycles of standard neoadjuvant THP regimen, consisting of a taxane, trastuzumab, and pertuzumab. After the initial 2-cycle treatment, tumor response will be evaluated by radiologic imaging and patient-derived organoid (PDO) drug sensitivity testing.
Patients with an inadequate response to THP are defined as those with \<50% tumor size reduction on imaging, or failure to reach the PDO sensitivity threshold (\<80% tumor cell killing for HER2+/HR- tumors; \<60% for HER2+/HR+ tumors). These non-responders will switch to receive 4 cycles of trastuzumab rezetecan (SHR-A1811), a novel HER2-targeted antibody-drug conjugate (ADC). Patients with a favorable response (≥50% tumor reduction or meeting the PDO threshold) will continue with an additional 4 cycles of THP.
The primary objective is to evaluate the pathologic complete response (pCR) rate in THP non-responders after switching to trastuzumab rezetecan. Secondary objectives include objective response rate (ORR), event-free survival (EFS), overall survival (OS), 3-year invasive disease-free survival (iDFS), and safety profiles of both treatment strategies. Outcomes in patients who continue THP will be described for exploratory purposes.
A total of 124 patients will be enrolled. This response-adapted, individualized strategy aims to provide an effective option for HER2-positive breast cancer patients with an inadequate early response to conventional THP neoadjuvant therapy.