Fulvestaciclib Combined With Anti-HER2 and Endocrine Therapy for HR+/HER2+ Advanced Breast Cancer

This phase II, multicenter, open‐label, randomized controlled trial (FACET study)evaluates the efficacy and safety of fulvestaciclib, a novel oral CDK4/6 inhibitor,combined with anti‐HER2 dual blockade (trastuzumab and pertuzumab, HP) and endocrinetherapy (ET) in hormone receptor‐positive (HR+) and HER2‐positive advanced breast cancer(ABC).Patients with HR+/HER2+ ABC without prior systemic therapy for advanced disease arerandomized in a 1:1:1 ratio into three arms, stratified by visceral metastasis status(yes vs. no) and metastatic type (de novo vs. recurrent).Arm A: After 4‐8 cycles of induction chemotherapy (taxane) plus HP, patients receivefulvestaciclib + HP + ET as maintenance therapy.Arm B: After 4‐8 cycles of induction chemotherapy (taxane) plus HP, patients receive HP +ET alone (without fulvestaciclib) as maintenance therapy.Arm C (exploratory): Patients receive upfront fulvestaciclib + HP + ET as first‐linetherapy without induction chemotherapy (chemo‐free).For premenopausal/perimenopausal patients, ovarian function suppression (OFS) is added inall arms. Treatment continues until disease progression, unacceptable toxicity,withdrawal of consent, or death.The primary endpoint is investigator‐assessed progression‐free survival (PFS) comparingArm A versus Arm B. Secondary endpoints include PFS (Arm A vs. Arm C), overall survival(OS), objective response rate (ORR), clinical benefit rate (CBR), duration of response(DoR), cumulative incidence of central nervous system (CNS) metastases, safety, andpatient‐reported outcomes (PROs).