On September 17, 2024, the U.S. Food and Drug Administration (FDA) approved ribociclib (Kisqali®) 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 with a high risk for recurrence. Additionally, FDA approved the ribociclib and letrozole co-pack (Kisqali® Femara® Co-Pack) for the same indication.
Efficacy of ribociclib with a nonsteroidal aromatase inhibitor (NSAI) was evaluated in NATALEE (NCT03701334), a randomized, open-label, multicenter trial involving 5,101 adults with HR-positive, HER2-negative early breast cancer. The trial included patients with:
- Any lymph node involvement (excluding microscopic)
- If no nodal involvement:
- Tumor size greater than 5 cm
- Tumor size 2–5 cm with either grade 2 disease with high genomic risk or Ki67 ≥ 20% or grade 3 disease
Participants were randomized 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 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), defined as randomization to the first occurrence of:
- Contralateral invasive breast cancer
- Death from any cause
- Distant recurrence
- Local or regional invasive breast recurrence
- 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 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 iDFS final analysis, overall survival data were immature.
For patients with early breast cancer, the most common adverse reactions, including laboratory abnormalities, reported in at least 20% of patients are decreased lymphocytes, leukocytes, neutrophils, hemoglobin, and platelets; increased alanine aminotransferase, aspartate aminotransferase, and creatinine; infections; headache; nausea; and fatigue.
For patients with advanced or metastatic breast cancer, the most common adverse reactions, including laboratory abnormalities, reported in at least 20% of patients are decreased leukocytes, neutrophils, hemoglobin, lymphocytes, platelets, and glucose serum; increased aspartate aminotransferase, gamma glutamyl transferase, alanine aminotransferase, and creatinine; infections; nausea; fatigue; diarrhea; vomiting; headache; constipation; alopecia; cough; rash; and back pain.
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 ribociclib and ribociclib and letrozole co-pack for the recommended dosages.
Ribociclib should now be refrigerated until dispensed to patients. After dispensing, healthcare providers should advise patients to store ribociclib at room temperature for up to two months.
The applicant used the Assessment Aid to facilitate the FDA’s review.
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 800-FDA-1088.
For assistance with single-patient applications for investigational oncology products, healthcare professionals should contact the Oncology Center of Excellence’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.