On September 17, 2024, the Food and Drug Administration approved ribociclib (Kisqali, Novartis Pharmaceuticals Corporation) with an aromatase inhibitor for the adjuvant treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage II and III early breast cancer at high risk of recurrence. Additionally, FDA also approved the ribociclib and letrozole co-pack (Kisqali Femara Co-Pack, Novartis Pharmaceuticals Corporation) for the same indication.

Full prescribing information for Kisqali and Kisqali Femara Co-Pack will be posted on Drugs@FDA.

Efficacy of ribociclib with a non-steroidal aromatase inhibitor (NSAI) was evaluated in NATALEE (NCT03701334), a randomized, open-label, multicenter trial in 5101 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 2 to 5 cm with either Grade 2 (and high genomic risk or Ki67 ≥ 20%) or Grade 3.

Participants were randomized (1:1) to receive ribociclib (400 mg) + NSAI or NSAI alone; patients could receive goserelin as indicated. Randomization was stratified by anatomic stage, prior chemotherapy (neoadjuvant versus adjuvant), menopausal status (premenopausal and males versus postmenopausal) and region (North America/Western Europe/Oceania versus rest of the world).

The main efficacy outcome measure was invasive disease-free survival (iDFS). iDFS 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 non-breast invasive cancer (excluding basal and squamous cell carcinomas of the skin).

A statistically significant improvement in iDFS was observed in the intent-to-treat patient population at an interim analysis. Efficacy results at the final iDFS analysis showed that iDFS at 36 months was 90.7% (95% CI: 89.3, 91.8) in the ribociclib + 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 iDFS final analysis, OS 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.

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.

Kisqali has newly updated storage conditions. Kisqali should now be refrigerated until dispensed to patients. After dispensing, healthcare providers should advise patients to store Kisqali at room temperature for up to 2 months.

This review used the Assessment Aid, a voluntary submission from the Applicant to facilitate the FDA's assessment.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA's MedWatch Reporting System or by calling 1-800-FDA-1088.

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