On September 17, the U.S. Food and Drug Administration (FDA) approved the CDK4/6 inhibitor ribociclib (Kisqali) with an aromatase inhibitor for the adjuvant treatment of adults with hormone receptor (HR)-positive, HER2-negative stage II and III early breast cancer at high risk of recurrence. The FDA also approved the ribociclib and letrozole co-pack (Kisqali Femara Co-Pack) for the same indication.
Efficacy and Safety
Efficacy of ribociclib with a nonsteroidal aromatase inhibitor (NSAI) was evaluated in the NATALEE trial (ClinicalTrials.gov identifier NCT03701334), a randomized, open-label, multicenter trial in 5,101 adults with HR-positive, HER2-negative early breast cancer. The trial included patients with any lymph node involvement (excluding microscopic nodal involvement), or if there was no nodal involvement, either tumor size > 5 cm, or tumor size of 2 to 5 cm with either grade 2 (and high genomic risk or Ki67 ≥ 20%) or grade 3.
Participants were randomly assigned (1:1) to receive ribociclib (400 mg) plus NSAI or NSAI alone; patients could receive goserelin as indicated. Randomization was stratified by anatomic stage, prior chemotherapy (neoadjuvant vs adjuvant), menopausal status (premenopausal and males vs postmenopausal) and region (North America/Western Europe/Oceania vs rest of the world).
The main efficacy outcome measure was invasive disease–free survival, which was defined as randomization to the first occurrence of the following: local or regional invasive breast recurrence, distant recurrence, death from any cause, contralateral invasive breast cancer, or secondary primary nonbreast invasive cancer (excluding basal and squamous cell carcinomas of the skin).
A statistically significant improvement in invasive disease–free survival was observed in the intent-to-treat patient population at an interim analysis. Efficacy results at the final invasive disease–free survival analysis showed that invasive disease–free survival at 36 months was 90.7% (95% confidence interval [CI] = 89.3–91.8) in the ribociclib plus NSAI arm and 87.6% (95% CI = 86.1–88.9) in the NSAI arm, with a hazard ratio of 0.749 (95% CI = 0.628–0.892). At the time of the invasive disease–free survival final analysis, overall survival was immature.
The adverse reactions observed on the NATALEE trial were consistent with the current safety profile for ribociclib in combination with an NSAI. The prescribing information provides additional safety information.
Dosing and Storage
In the adjuvant treatment setting, the recommended ribociclib dose is 400 mg (two 200-mg film-coated tablets) taken orally, once daily for 21 consecutive days followed by 7 days off in 28-day treatment cycles. Refer to the prescribing information for the recommended dosage of the aromatase inhibitor.
Ribociclib has newly updated storage conditions and should now be refrigerated until dispensed to patients. After dispensing, health-care providers should advise patients to store ribociclib at room temperature for up to 2 months.
