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

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.