FDA approved Kisqali (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.
Kisqali 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 (PFS) compared to letrozole alone at the first pre-planned interim analysis. Kisqali was reviewed and approved under the FDA Breakthrough Therapy designation and Priority Review programs.
FDA approval is based on the superior efficacy and demonstrated safety of Kisqali 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 Kisqali 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) vs. 14.7 months (95% CI: 13.0-16.5 months); HR=0.556 (95% CI: 0.429-0.720); p<0.0001).
More than half of patients taking Kisqali 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 Kisqali 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 Hortobagyi, professor of medicine, Department of Breast Medical Oncology, MD Anderson Cancer Center, 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.” Kisqali was developed by the Novartis Institutes for BioMedical Research under a research collaboration with Astex Pharmaceuticals.
Prescribing information for Kisqali is posted at https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/kisqali.pdf
