Trastuzumab Rezetecan Followed by Pyrotinib, Fulvestrant, and Dalpiciclib in HR-Positive, HER2-Positive Advanced Breast Cancer

The purpose of this clinical trial is to evaluate whether, in patients with hormone receptor-positive (HR-positive) and HER2-positive advanced breast cancer whose disease has progressed after trastuzumab-based therapy, switching to pyrotinib, fulvestrant, and dalpiciclib after induction with trastuzumab rezetecan-among those without disease progression-is superior to continued treatment with trastuzumab rezetecan. The three medicines are pyrotinib (a medicine that blocks HER2 and similar signals), fulvestrant (a hormone therapy), and dalpiciclib (a medicine that slows cancer cell division). The primary question this study aims to answer is: Does switching to pyrotinib, fulvestrant, and dalpiciclib prolong the time participants live without their cancer worsening compared with continued treatment with trastuzumab rezetecan? The study will also assess overall survival, tumor response to treatment, and adverse events. Researchers will compare the three-medicine combination with continued trastuzumab rezetecan. Participants will: Receive trastuzumab rezetecan once every 3 weeks for 6 cycles. If the cancer has not worsened after these 6 cycles, be randomly assigned to receive either the three-medicine combination or continued trastuzumab rezetecan. Undergo imaging scans every 6 weeks during the first 24 weeks and every 9 weeks thereafter to assess the cancer. Undergo blood tests, cardiac assessments, and other safety evaluations during treatment and follow-up.