elderly ER/HER2 positive breast cancer
Palbociclib with hormonal therapy and HERS blockade vs Paclitaxel with HER2 blockade
Mandatory pre-treatment biopsy collected as an FFPE specimen
To explore the interaction between the RBsig status (HIGH or LOW) and treatment activity of palbociclib + letrozole versus paclitaxel when given with trastuzumab plus pertuzumab for ER+/HER2+ primary BC.
Histologically confirmed invasive breast cancer, with the following characteristics:
Early breast cancer with tumor size >1 cm (as measured by at least one of the required examination methods of clinical examination, mammography and ultrasonography); No clinical evidence of regional lymph node metastasis (N0), or, nodal involvement limited to clinically detectable metastasis to movable ipsilateral level I, II axillary lymph node(s) (N1); No evidence of metastasis (M0).
Female aged 65 years or older
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Primary tumor must have positive estrogen receptor (ER) ≥10%
Primary tumor must be HER2-positive (by IHC and/or ISH)
Baseline LVEF ≥55% measured by Echocardiography (preferred) or MUGA scan
Normal hematologic status: Absolute neutrophil count ≥1500/mm3 (1.5 × 109/L); Platelets ≥100 × 109/L; Hemoglobin ≥9 g/dL (≥90 g/L).
Normal renal function: serum creatinine ≤1.5 ULN
Normal liver function: Serum total bilirubin ≤1.5 × upper limit of normal (ULN). In the case of known Gilbert's syndrome, a higher serum total bilirubin (<2 × ULN) is allowed; AST or ALT ≤2.5 × ULN; Alkaline phosphatase ≤2.5 × ULN.
Written Informed Consent (IC) must be signed and dated by the patient and the Investigator prior to randomization.
The patient has been informed of and agrees to data transfer and handling, in accordance with national data protection guidelines.
The patient agrees in writing to make tumor (mandatory diagnostic core biopsy and surgical specimen) available for submission for central pathology review and to conduct translational studies as part of this protocol.
Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or skin nodules) (T4 according to AJCC 8th edition cancer staging TNM)
Inflammatory breast cancer
Bilateral invasive breast cancer
Received any prior treatment for primary invasive breast cancer
Any active tumor of non-breast-cancer histology
Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina pectoris, ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (NYHA functional classification ≥II), cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism.
Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety
Contraindications or known hypersensitivity to any of the trial medications or excipients
Treatment with any investigational agents within 30 days prior to expected start of trial treatment
Any GI disorder that may affect absorption of oral medications, such as malabsorption syndrome or status post major bowel resection