FDA Approves Ribociclib as Initial Therapy for Hormone Receptor–Positive, HER2-Negative Advanced or Metastatic Breast Cancer

On March 13, 2017, the U.S. Food and Drug Administration (FDA) approved ribociclib (Kisqali), a cyclin-dependent kinase (CDK) 4/6 inhibitor, in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.


Approval was based on a randomized, double-blind, placebo-controlled, international clinical trial (MONALEESA-2), in post-menopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer who received no prior therapy for advanced disease. A total of 668 patients were randomized to receive either ribociclib plus letrozole (n = 334) or placebo plus letrozole (n = 334). Ribociclib 600 mg or placebo was administered orally once daily for 21 consecutive days, followed by 7 days off, with letrozole 2.5 mg administered orally once daily for 28 days. Treatment continued until disease progression or unacceptable toxicity.

A preplanned interim efficacy analysis demonstrated an improvement in progression-free survival (investigator-assessed) with hazard ratio of 0.556 (95% confidence interval [CI] = 0.429–0.720; P < .0001). The estimated median progression-free survival had not been reached in the ribociclib-containing arm and was 14.7 months in the placebo-containing arm. Objective response rate in patients with measurable disease was 52.7% (95% CI = 46.6–58.9) in the ribociclib-plus-letrozole arm and 37.1% (95% CI = 31.1–43.2) in the placebo-plus-letrozole arm. Overall survival data are immature.

The most common adverse reactions observed in 20% or more of patients taking ribociclib were neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, and back pain. The most common grade 3 or 4 adverse reactions (reported in > 2%) were neutropenia, leukopenia, abnormal liver function tests, lymphopenia, and vomiting. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner.

The recommended starting dose of ribociclib is 600 mg orally (three 200-mg tablets) taken once daily with or without food for 21 consecutive days followed by 7 days off treatment.

Full prescribing information for ribociclib is available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209092s000lbl.pdf.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.