Study of Efficacy and Safety of LEE011 in Postmenopausal Women With Advanced Breast Cancer

Exclusion Criteria

• •1. The patient had received any CDK4/6 inhibitor.
• •2. The patient had received any prior systemic anti-cancer therapy (including hormonal therapy and chemotherapy) for advanced breast cancer.
• •Note:
• •* Patients who had received (neo) adjuvant therapy for breast cancer were eligible. If the prior neo (adjuvant) therapy included letrozole or anastrozole, the disease-free interval had to be greater than 12 months from the completion of treatment until randomization.
• •* Patients who had received ≤ 14 days of letrozole or anastrozole for advanced disease prior to randomization were eligible.
• •* Any prior (neo) adjuvant anti-cancer therapy had to be stopped at least 5 half-lives or 7 days, whichever was longer, before randomization.
• •3. The patient was concurrently using other anti-cancer therapy.
• •4. The patient had a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer, or curatively resected cervical cancer.
• •5. The patient had active cardiac disease or a history of cardiac dysfunction, including any of the following:
• •* History of angina pectoris, symptomatic pericarditis, or myocardial infarction within 12 months prior to study entry.
• •* History of documented congestive heart failure (New York Heart Association functional classification III-IV).
• •* Documented cardiomyopathy.
• •* The patient had a Left Ventricular Ejection Fraction (LVEF) \< 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO).
• •* History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months.
• •* On screening, any of the following cardiac parameters: bradycardia (heart rate \< 50 at rest), tachycardia (heart rate \> 90 at rest), PR interval \> 220 msec, QRS interval \>109 msec, or QTcF \>450 msec.
• •* Systolic blood pressure \>160 or \<90 mmHg.
• •6. The patient was currently receiving any of the following medications and could not be discontinued 7 days prior to the start of treatment:
• •* Medications known to be strong inducers or inhibitors of CYP3A4.
• •* Medications known to have a risk of prolonging the QT interval or inducing Torsades de Pointes.
• •* Medications with a narrow therapeutic window and predominantly metabolized through CYP3A4.
• •* Herbal preparations/medications.