FDA Grants Approval to Ribociclib With Aromatase Inhibitor and Letrozole Co-Pack for Adjuvant Treatment of HR-Positive HER2-Negative High-Risk Breast Cancer

On September 17, 2024, the US Food and Drug Administration (FDA) granted approval to ribociclib (Kisqali, Novartis) 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, they approved the ribociclib and letrozole co-pack (Kisqali Femara Co-Pack, Novartis) for this patient group. This approval was based on results from the NATALEE study.

This randomized, open-label, multicenter trial included 5,101 patients with HR-positive, HER2-negative early breast cancer. The trial centered on 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. These participants were randomized 1-to-1 to receive ribociclib at 400 mg plus an NSAI, or NSAI alone. Participating patients could also receive goserelin as indicated.

The randomization was stratified by anatomic stage, neoadjuvant versus adjuvant prior chemotherapy, premenopausal and males versus postmenopausal, and region. The study’s main efficacy outcome measure was invasive disease-free survival (iDFS), 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 non-breast invasive cancer, a category which excluded basal and squamous cell skin carcinomas.

At an interim analysis of the data, a statistically significant improvement in iDFS was demonstrated in the intent-to-treat patient population. The efficacy results at the final iDFS analysis revealed that iDFS at 36 months was 90.7% (95% confidence interval [CI], 89.3 to 91.8) in the ribociclib plus NSAI arm, and 87.6% (95% CI, 86.1 to 88.9) in the NSAI arm, with a hazard ratio (HR) of 0.749 (95% CI, 0.628 to 0.892). At the time of the iDFS final analysis, the overall survival (OS ) data was not mature.

As for treatment-related adverse events, the reactions observed on the NATALEE trial matched the current safety profile for ribociclib in combination with an NSAI. The prescribing information provides additional safety information. There are also has newly updated storage conditions for ribociclib, which should be refrigerated until dispensed to patients; patients may then store ribociclib at room temperature for up to 2 months.

Source:

FDA approves Kisqali with an aromatase inhibitor and Kisqali Femara co-Pack for early high-risk breast cancer. US Food and Drug Administration. Accessed September 17, 2024.  https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-kisqali-aromatase-inhibitor-and-kisqali-femara-co-pack-early-high-risk-breast-cancer