The U.S. Food and Drug Administration has approved Kisqali (ribociclib), in combination with an aromatase inhibitor as first-line treatment for post-menopausal and hormone-positive, HER2-negative metastatic breast cancer patients.

The approval was granted to Novartis under the FDA’s breakthrough therapy designation and priority review programs. It was based on data from a Phase 3 trial assessing the safety and efficacy Kisqali plus Femara (letrozole) versus Femara alone, which met its primary endpoint of progression-free survival at interim analysis.

Kisqali is a selective inhibitor of the CDK4/6 proteins, which when overactive can lead to unregulated proliferation of cancer cells.  Targeting CDK4/6 with high precision may halt the uncontrolled replication of cancer cells.

The recent approval was based on data from the MONALEESA-2 Phase 3 trial (NCT01958021), a randomized and double-blind study that enrolled 668 patients with postmenopausal HR-positive, HER2-negative advanced breast cancer to study Kisqali plus Femara as first-line therapy.

Participants were randomized to receive Kisqali (600 mg a day, in monthly cycles marked by three weeks of treatment with a one-week pause) in combination with Femara ( 2.5 mg/day), or a placebo plus Femara.

At the interim analysis, the trial had met its primary endpoint, with patients on Kisqali showing a 44 percent reduction in the risk of disease progression. While those on Femala monotherapy had a median progression-free survival (PFS) of 14.7 months at this point, those in the Kisqali treatment group had not yet reached median PFS — more than half of these patients remained disease-free at the time of the analysis.

At a subsequent analysis, with an additional 11 months of follow-up and progression events, data showed that Kisqali-treated patients remained disease free nearly nine months longer than those given only Femara. The median PFS for the Kisqali arm was 25.3 months versus 16.0 months for the control group. Overall survival data is not yet available.

“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,” Gabriel Hortobagyi, MD, the trial’s principal investigator, said in a press release.

“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,” added Hortobagyi, a professor of medicine with the Department of Breast Medical Oncology at the University of Texas MD Anderson Cancer Center.