FDA Approves Ribociclib Plus Aromatase Inhibitor as First-Line Treatment for Metastatic, Advanced Breast Cancer

The FDA granted approval to ribociclib (Kisqali) in combination with aromatase inhibitor as first-line treatment for hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2) advanced or metastatic breast cancer.

Ribociclib, formerly known as LEE011, is a selective cyclin-dependent kinases (CDK) inhibitor designed to slow the progression of cancer by inhibiting the proteins CDK4 and CDK6, according to a Novartis press release.

The approval is based on data from a first-line phase 3 trial that met its primary endpoint early, demonstrating statistically significant improvement in progression-free survival (PFS) compared with letrozole monotherapy at the first pre-planned interim analysis.

Ribociclib was reviewed and approved under the FDA Breakthrough Therapy designation and Priority Review programs, according to the release.

“Kisqali [sic] is emblematic of the innovation that Novartis continues to bring forward for people with HR+/HER2-metastatic breast cancer,” Bruno Stringini, ceo of Novartis Oncology, said in the release. “We at Novartis are proud of the comprehensive clinical program for [ribociclib] that has led to today’s approval and the new hope this medicine represents for patients and their families.”

The pivotal phase 3 MONALEESA-2 trial included 668 postmenopausal women with HR+/HER2- advanced or metastatic breast cancer who received no prior systemic therapy for their disease.

The results of the study showed that ribociclib plus aromatase inhibitor letrozole reduced the risk of progression or death by 44% compared with letrozole monotherapy.

More than half of patients administered 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 an additional 11-month follow-up and progression events, the findings showed a median PFS of 25.3 months for ribociclib plus letrozole and 16 months for letrozole monotherapy.

The overall survival data are not yet mature at this time and will become available at a later date, according to the release.

“In the MONALEESA-2 trial, ribociclib plus letrozole reduced the risk of disease progression or death by 44% 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%,” principal investigator Gabriel N. Hortobagyi, MD, said in the release. “This is a significant result for women with this serious form of breast cancer. 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.”

Ribociclib is taken with or without food as a once-daily oral dose of 600 mg (three 200 mg tablets) for 3 weeks, followed by 1 week off treatment. The drug is taken in combination with 4 weeks of any aromatase inhibitor.