Novartis Reports Positive Topline Results for NATALEE, Phase 3 Trial of Ribociclib in Early Breast Cancer

Novartis today announced that the phase 3 NATALEE trial evaluating its CDK4/6 inhibitor ribociclib (Kisqali) in early breast cancer, had met its primary end point in this pivotal study. Results will be presented at an upcoming scientific meeting and submitted to FDA and to regulatory agencies in other countries, according to the company’s statement.

NATALEE enrolled patients with stage II and stage III HR+/HER2- early breast cancer (EBC), regardless of nodal involvement. The primary end point, invasive disease-free survival, measures whether a patient’s cancer has returned. According to a statement from Novartis, ribociclib plus endocrine therapy significantly reduced the risk of disease recurrence compared with standard endocrine therapy alone in the adjuvant setting.

Officials from Novartis said NATALEE represents the broadest patient population of any CDK4/6 inhibitor trial to date. EBC represents more than 90% of patients with breast cancer; citing data published in the New England Journal of Medicine, officials said 30% to 60% of the patient population represented in the NATALEE trial currently remains at risk of breast cancer recurrence with endocrine therapy only.

“While most patients are diagnosed and treated early with the aim to cure breast cancer, the risk of cancer returning, often as metastatic disease, peaks within 3 years after diagnosis, but never goes away completely,” Dennis J. Slamon, MD, who is director of Clinical/Translational Research for the University of California, Los Angeles Jonsson Comprehensive Cancer Center, said in the statement.

Slamon is chairman and executive director of Translational Research In Oncology (TRIO) and the lead investigator for NATALEE. In this trial, patients in the study drug arm were given ribociclib alongside endocrine therapy for 3 years.

"There is a critical need for new, well-tolerated options that keep patients cancer-free without disrupting quality of life,” he said. “It is extremely encouraging that this study met its primary endpoint.”

The NATALEE study protocol calls for ongoing follow-up to evaluate long-term outcomes, including overall survival.

The most recent update to National Comprehensive Cancer Network (NCCN) clinical guidelines for breast cancer, released in January 2023, recommends ribociclib as the only Category 1 preferred CDK4/6 inhibitor for first-line treatment of patients with HR+/HER2- metastatic breast cancer when combined with an aromatase inhibitor.