Palbociclib in Molecularly Characterized ER-positive/HER2-negative Metastatic Breast Cancer

Inclusion Criteria

• Female gender
• Age ≥ 18 years
• Postmenopausal, defined as women with:
• Prior bilateral surgical oophorectomy; or
• Amenorrhea and age ≥ 60 years; or
• Age 3 months.
• Hematological status:
• Absolute neutrophil count ≥ 1.5 × 109/L
• Platelet count ≥ 100 × 109/L
• Hemoglobin ≥ 9 g/dL
• Hepatic status:
• Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN).
• AST and ALT ≤ 2.5 × ULN; if the patient has liver metastases, ALT and AST must be ≤ 5 × ULN.
• Glucose in normal range, or well-controlled diabetes defined as an HbA1c level ≤ 7.5%.
• Renal status:
• Creatinine ≤ 1.5 ×ULN or creatinine clearance > 60 ml/min.
• International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulant.
• Ability to swallow oral medication.

Exclusion Criteria

• Prior use of fulvestrant or any CDK inhibitor.
• More than one prior line of chemotherapy for metastatic or locally relapsed disease.
• Previous or current non-breast malignancies within the last 5 years, with the exception of in situ carcinoma of the cervix, and adequately treated basal cell or squamous cell carcinoma of the skin.
• Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth.
• 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 ≥3), cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism.
• QTc exceeding 480msec, family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP).
• Uncontrolled electrolyte disorders that can reinforce the QT-prolonging effect of the drug (e.g., hypocalcemia, hypokalemia, hypomag¬nesemia).
• Known history of HIV seropositivity. HIV screening is not required at baseline.
• Uncontrolled diabetes defined as HbA1c level > 7.5%.
• Concurrent disease or familial, sociological or geographical condition that would make the patient inappropriate for trial participation or any serious medical disorder that would interfere with the patient's safety.
• Dementia, altered mental status, or any psychiatric condition that would prevent the understanding or rendering of Informed Consent.
• Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of fulvestrant.
• Treatment with an investigational agent in the 4 weeks before enrollment.
• Concurrent treatment with any of the drugs not permitted
• Adverse events (except alopecia) from previous systemic cancer therapy, radiotherapy or surgery have not recovered to CTCAE v4.0 grade 1 or resolved prior to enrollment.