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The FDA has approved ribociclib, formerly known as LEE011, in combination with an aromatase inhibitor as initial endocrine-based therapy for treatment of postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer. Ribociclib is a CDK4/6 inhibitor approved based on a first-line phase III trial that met its primary endpoint early, demonstrating statistically significant improvement in progression-free survival compared to letrozole alone at the first pre-planned interim analysis. Ribociclib was reviewed and approved under the FDA Breakthrough Therapy Designation and Priority Review programs. The FDA approval is based on the superior efficacy and demonstrated safety of ribociclib plus letrozole versus letrozole alone in the pivotal phase III MONALEESA-2 trial. The trial, which enrolled 668 postmenopausal women with HR+/HER2- advanced or metastatic breast cancer who received no prior systemic therapy for their advanced breast cancer, showed that ribociclib plus an aromatase inhibitor, letrozole, reduced the risk of progression or death by 44 percent over letrozole alone (median PFS not reached [95% CI: 19.3 months-not reached] versus 14.7 months (95% CI: 13.0-16.5 months); HR=0.556 (95% CI: 0.429-0.720); p<0.0001)

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More than half of patients taking ribociclib plus letrozole remained alive and progression free at the time of interim analysis; therefore, median PFS could not be determined. At a subsequent analysis with additional 11-month follow-up and progression events, a median PFS of 25.3 months for ribociclib plus letrozole and 16.0 months for letrozole alone was observed. Overall survival data is not yet mature and will be available at a later date.


"In the MONALEESA-2 trial, ribociclib plus letrozole reduced the risk of disease progression or death by 44 percent over letrozole alone, and more than half of patients (53%) with measurable disease taking ribociclib plus letrozole experienced a tumor burden reduction of at least 30 percent. This is a significant result for women with this serious form of breast cancer," said Gabriel N. Hortobagyi, MD, Professor of Medicine, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, and MONALEESA-2 principal investigator. "These results affirm that combination therapy with a CDK4/6 inhibitor like ribociclib and an aromatase inhibitor should be a new standard of care for initial treatment of HR+ advanced breast cancer."