Adding Kisqali (ribociclib) to a nonsteroidal aromatase inhibitor helped patients with hormone receptor–positive, HER2-negative early breast cancer live longer without their disease returning, according to five-year results from the NATALEE study presented at the 2025 ESMO Congress.
The median follow-up was 55.4 months. The 36-month iDFS rates in the Kisqali and aromatase inhibitor–alone arms were 90.8% and 88%, respectively; the 60-month iDFS rates were 85.5% and 81%, respectively.
“Kisqali plus an aromatase inhibitor continues to reduce the risk of recurrence beyond a three-year treatment window, supporting its use as adjuvant therapy in a broad population of patients with hormone receptor–positive, HER2-negative early breast cancer at high risk of recurrence,” Dr. John Crown, a professor and consultant medical oncologist at St. Vincent’s University Hospital in Dublin, Ireland, said during the presentation.
Notably, in September 2024, the FDA approved adjuvant Kisqali in combination with an aromatase inhibitor for the treatment of patients with hormone receptor–positive, HER2-negative stage 2 and 3 early breast cancer at high risk of recurrence, including those with node-negative disease. The regulatory decision was supported by prior data from NATALEE.
Glossary
Invasive disease-free survival (iDFS): time after treatment during which a patient has no return of invasive breast cancer or new cancer in another part of the body.
Distant disease-free survival (DDFS): time after treatment when a patient remains free of breast cancer that has spread to distant parts of the body.
Overall survival (OS): time from treatment start or diagnosis until death from any cause.
Relapse-free survival: time after treatment when a patient has no local, regional, or distant return of breast cancer.
Distant recurrence-free survival: time after treatment when a patient has no cancer return in distant organs or tissues.
What Were the Design Features of NATALEE?
NATALEE was an open-label, multicenter, randomized trial that enrolled adult patients with stage 2 and 3 hormone receptor–positive, HER2-negative early breast cancer. Patients were permitted to have received prior endocrine therapy up to 12 months before enrollment.
Patients with anatomical stage 2A disease needed to have N0 disease that was grade 2 and had evidence of high risk, defined by a Ki-67 score of at least 20%, an Oncotype DX Breast Recurrence Score of at least 26 or high-risk status via genomic risk profiling, and grade 3 disease; patients with N1 disease in this anatomical stage were also eligible. Patients with anatomical stage 2B disease needed to have N0 or N1 disease. Patients with anatomical stage 3 disease could have N0 through N3 disease.
Eligible patients were randomly assigned one-to-one to receive Kisqali at 400 mg per day via a three-weeks-on, one-week-off dosing schedule for three years in combination with a nonsteroidal aromatase inhibitor for at least five years, or a nonsteroidal aromatase inhibitor alone.
The primary end point was iDFS using Standardized Definitions for Efficacy End Points criteria. Secondary end points included relapse-free survival, distant disease–free survival (DDFS), overall survival, patient-reported outcomes, safety and tolerability, and pharmacokinetic measures. Distant recurrence–free survival, as well as gene expression and alterations in circulating tumor DNA/ctRNA samples, were also evaluated as exploratory end points.
At the May 28, 2025, data cutoff, 62.8% of patients in the combination arm had completed three years of treatment with Kisqali, and 36.5% of patients had completed five years of aromatase inhibitor therapy. Aromatase inhibitor treatment was ongoing in 27.1% of patients, and 51.4% of patients remained in the follow-up phase.
In the aromatase inhibitor–alone arm, 34.4% of patients had completed five years of treatment. Therapy was ongoing in 23.7% of patients, and 50.3% of patients were in the follow-up phase.
What Were the Safety and Additional Efficacy Data From NATALEE?
At the time of this analysis, all patients had stopped receiving therapy for a median of two years. No new safety signals were identified with Kisqali, including no delayed toxicities or cumulative effects following therapy. Since the previous four-year exploratory analysis, with an additional follow-up of 12.9 months, three patients had died in the combination arm due to side effects, and two others had died in the control arm due to side effects. Three percent of patients had developed secondary primary malignancies in the control arm compared with 2.7% of those in the combination arm.
At a median follow-up of 56.5 months, the five-year overall survival rates in the investigational and control arms were 94.1% versus 92.5%, respectively. At a median follow-up of 55.5 months, a significant benefit in terms of DDFS was reported in favor of the Kisqali arm. A similar benefit in terms of distant recurrence–free survival was also observed in favor of the investigational arm.
Patients experienced an iDFS benefit with the addition of Kisqali to an aromatase inhibitor versus an aromatase inhibitor alone, irrespective of having N0 or N-positive nodal status. Notably, an iDFS benefit with Kisqali was reported across all prespecified patient subgroups.
“For the first time, in this five-year analysis, a clinically meaningful risk reduction of approximately 30% was seen for DDFS or death and distant recurrence–free survival or death. Kisqali plus an aromatase inhibitor showed a continued numerical trend for improved overall survival,” Crown emphasized in his conclusion.
References
- “Adjuvant ribociclib plus nonsteroidal aromatase inhibitor therapy in patients with HR+/HER2– early breast cancer: NATALEE five-year outcomes” by Dr. John Crown, et al., ESMO Congress.
- “FDA approves Novartis Kisqali to reduce risk of recurrence in people with HR+/HER2- early breast cancer,” Novartis.
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