Ribociclib is an oral CDK4/6 inhibitor. Its pharmacologic activity is based on inhibition of CDK4 and CDK6, enzymes involved in cell-cycle progression.
Pharmacokinetics
Following oral administration, the median time to maximum concentration is approximately 1–4 hours. The mean absolute bioavailability after a single 600 mg dose is approximately 65.8%. A high-fat meal does not produce clinically meaningful differences in ribociclib exposure.
Metabolism
Ribociclib undergoes extensive metabolism. CYP3A contributes importantly to its metabolism, making CYP3A inhibitors and inducers clinically relevant interaction considerations.
Half-life
The mean plasma effective half-life at steady state after 600 mg dosing is approximately 32 hours. Reported apparent terminal half-life values in healthy adults have ranged from approximately 29.7 to 54.7 hours.
Elimination
After a radiolabeled dose, most recovered radioactivity was found in feces, with a smaller proportion recovered in urine.
Pharmacology summary
| Feature | Information |
|---|---|
| Drug class | CDK4/6 inhibitor |
| Primary targets | CDK4 and CDK6 |
| Route | Oral |
| U.S. tablet strength | 200 mg |
| Time to peak concentration | Approximately 1–4 hours |
| Mean effective half-life at 600 mg steady state | Approximately 32 hours |
| Major metabolic relevance | CYP3A |
Clinical evidence
The MONALEESA program established evidence for ribociclib in HR-positive/HER2-negative advanced or metastatic breast cancer. MONALEESA-2 demonstrated an overall-survival benefit for ribociclib plus letrozole compared with letrozole alone.
MONALEESA-3 demonstrated longer overall survival with ribociclib plus fulvestrant compared with fulvestrant alone in the studied population.
MONALEESA-7 evaluated premenopausal and perimenopausal patients receiving ovarian suppression and endocrine therapy and also demonstrated an overall-survival benefit.
The NATALEE program provided evidence supporting the early-breast-cancer indication, with regulatory authorities subsequently authorizing ribociclib for selected HR-positive/HER2-negative early breast cancer populations.
Limitations of clinical evidence
Clinical-trial results describe study populations and cannot predict an individual patient’s response. Differences in tumor characteristics, treatment history, comorbidities and treatment combinations can affect outcomes.