FDA Expands Approval of Ribociclib to Early Breast Cancer

The FDA on Tuesday approved ribociclib (Kisqali) in combination with endocrine therapy as adjuvant treatment for early high-risk breast cancer.

Already approved in the metastatic setting, the CDK4/6 inhibitor is now also indicated for patients with stages II-III disease who have hormone receptor (HR)-positive/HER2-negative tumors and a high risk for recurrence following surgery.

The drug joins abemaciclib (Verzenio) as approved CDK4/6 inhibitors in this setting, but the broader indication for ribociclib — which includes node-negative (N0) disease — roughly doubles the population of early breast cancer patients eligible for adjuvant therapy with a CDK4/6 inhibitor, according to drugmaker Novartis.

In the NATALEE trial of more than 5,100 patients with early-stage breast cancer, 3 years of adjuvant treatment with ribociclib plus a non-steroidal aromatase inhibitor reduced the risk of disease recurrence by 25% versus an aromatase inhibitor alone. At 3 years, rates of invasive disease-free survival (iDFS) were 90.7% and 87.6%, respectively (HR 0.749, 95% CI 0.628-0.892, P=0.0006).

New data from the phase III trial reported at the annual European Society for Medical Oncology congress showed a deeper iDFS benefit as well (HR 0.715, 95% CI 0.609-0.840, P<0.0001), with a consistent effect across subgroups; overall survival data remain immature.

“The FDA approval of Kisqali for this early breast cancer population, including those with N0 disease, is a pivotal moment in improving our approach to care,” investigator Dennis Slamon, MD, of the University of California Los Angeles Jonsson Comprehensive Cancer Center, said in a press release from Novartis. “Today’s approval allows us to offer treatment with a CDK4/6 inhibitor to a significantly broader group of people as a powerful tool that, combined with endocrine therapy, can help further minimize their risk of cancer returning.”

FDA also approved a ribociclib and letrozole co-pack (Kisqali Femara Co-Pack) for the same indication.

NATALEE included patients either with lymph node involvement, excluding microscopic nodal involvement; and those without lymph node involvement but with tumors over 5 cm or tumors 2-5 cm classified as either Grade 3 or Grade 2 with high genomic risk or a Ki67 score of 20% or greater.

Adverse events (AEs) in the study were consistent with the known safety profile of the CDK4/6 inhibitor in combination with a non-steroidal aromatase inhibitor, the FDA stated. Grade 3/4 AEs of special interest with the combination included neutropenia (44.3%), liver-related AEs (8.6%), and QT prolongation (1%).

The agency also noted that ribociclib, an oral drug, has 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,” the FDA stated.

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