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 endocrine therapy (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 are randomized 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 receive fulvestaciclib + 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-line therapy without induction chemotherapy (chemo-free).
For premenopausal/perimenopausal patients, ovarian function suppression (OFS) is added in all arms. Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or death.
The primary endpoint is investigator-assessed progression-free survival (PFS) comparing Arm 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, and patient-reported outcomes (PROs).
Age ≥ 18 years, with inoperable locally advanced or recurrent/metastatic breast cancer not amenable to curative-intent therapy.
Histologically or cytologically confirmed hormone receptor-positive (HR+) and HER2-positive (HER2+) breast cancer. HR+ is defined as estrogen receptor (ER) and/or progesterone receptor (PR) positivity with ≥1% of invasive tumor cells positive by immunohistochemistry (IHC). HER2+ is defined as IHC 3+ or IHC 2+ with in situ hybridization (ISH) positivity.
No prior systemic therapy for advanced breast cancer, including endocrine therapy, chemotherapy, anti-HER2 therapy, or any CDK4/6 inhibitor.
Patients may have received neoadjuvant or adjuvant therapy. If prior endocrine therapy was received in the neoadjuvant/adjuvant setting, the disease-free interval from completion of endocrine therapy to randomization must be ≥12 months. If prior anti-HER2 therapy was received, the disease-free interval from completion of anti-HER2 therapy to randomization must be ≥6 months.
Inflammatory breast cancer.
Leptomeningeal disease.
Active brain metastases (patients with asymptomatic brain metastases, or clinically stable and not requiring steroids or other CNS-directed therapy for ≥4 weeks are eligible).
Diagnosis of any other malignancy, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix that has been definitively treated.
Fudan University
Lead sponsor
Shanghai Henlius Biotech Co., Ltd.
Collaborator