Palbociclib in Combination With Fulvestrant or Letrozole in Patients With ER+, HER2- Advanced Breast Cancer

Inclusion Criteria

• Women 18 years or older with metastatic or locally advanced disease, not amenable to curative therapy
• Confirmed diagnosis of HR+/HER2- breast cancer
• Post-menopausal status
• No prior chemotherapy line in the metastatic setting
• Measurable disease defined by RECIST version 1.1, or non-measurable disease
• Eastern Cooperative Oncology Group (ECOG) PS 0-1
• Adequate organ and marrow function, resolution of all toxic effects of prior therapy or surgical procedures
• Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCICTCAE version 4.0 Grade equal or minor than 1

Exclusion Criteria

• ER or HER2 unknown disease
• HER2 positive disease based on local laboratory results
• Locally advanced breast cancer candidate for a radical treatment
• Prior (neo)adjuvant endocrine treatment with DFI ≤ 12-months from completion of treatment.
• Patients with rapidly progressive visceral disease or visceral crisis.
• Major surgery within 4 weeks of start of study drug
• Patients with an active, bleeding diathesis
• Serious concomitant systemic disorder incompatible with the study
• Are unable to swallow tablets
• Chronic daily treatment with corticosteroids with a dose of ≥ 10mg/day methylprednisolone equivalent
• Known active uncontrolled or symptomatic CNS metastases
• Known hypersensitivity to letrozole, fulvestrant or any of their excipients, or to any PD-0332991 excipients
• QTc > 480 msec on basal assessments, personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes
• Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug