Kisqali with an aromatase inhibitor and Kisqali Femara Co-Pack is approved by the USFDA for early high-risk breast cancer

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

The effectiveness of ribociclib in conjunction with a non-steroidal aromatase inhibitor (NSAI) was assessed in NATALEE (NCT03701334), a randomized, open-label, multicenter trial involving 5,101 adults with HR-positive, HER2-negative early breast cancer. The trial encompassed patients with any lymph node involvement (excluding microscopic nodal involvement), or in the absence of nodal involvement, those with tumor size above 5 cm, or tumor size between 2 to 5 cm accompanied by either Grade 2 (with high genomic risk or Ki67 ≥ 20%) or Grade 3 tumors.

Participants were randomized in a 1:1 ratio to receive ribociclib (400 mg) along with a non-steroidal aromatase inhibitor (NSAI) or NSAI alone; goserelin could be administered as clinically necessary. Randomization was stratified by anatomical stage, prior chemotherapy (neoadjuvant versus adjuvant), menopausal status (premenopausal and male against postmenopausal), and area (North America/Western Europe/Oceania versus the rest of the globe).

The primary effectiveness outcome measure was invasive disease-free survival (iDFS). iDFS was defined as the randomization to the initial occurrence of any of the following events:

Local or regional invasive breast recurrence

Distant recurrence

Mortality from any cause

Contralateral invasive breast cancer

Secondary primary non-breast invasive cancer (excluding basal and squamous cell carcinomas of the skin)

An interim study revealed a statistically significant enhancement in iDFS within the intent-to-treat patient population. The final iDFS analysis revealed that the iDFS at 36 months was 90.7% (95% CI: 89.3, 91.8) in the ribociclib + NSAI group and 87.6% (95% CI: 86.1, 88.9) in the NSAI group, yielding a hazard ratio of 0.749 (95% CI: 0.628, 0.892). At the time of the final analysis of iDFS, the OS was underdeveloped.

The adverse effects noted in the NATALEE trial aligned with the existing safety profile of ribociclib in conjunction with a non-steroidal aromatase inhibitor (NSAI). The prescription information offers supplementary safety details.

In the adjuvant treatment context, the prescribed ribociclib dosage is 400 mg (two 200 mg film-coated tablets) administered orally once day for 21 consecutive days, succeeded by a 7-day hiatus among 28-day treatment cycles. Consult the medication label for the advised dosage of the aromatase inhibitor.

Kisqali has recently revised its storage conditions. Kisqali must now be stored in a refrigerator until administered to patients. Following dispensing, healthcare practitioners should instruct patients to maintain Kisqali at room temperature for a duration of up to 2 months.