TOPLINE:

Ribociclib plus nonsteroidal aromatase inhibitor therapy reduces the risk for invasive disease recurrence by 28.5% compared with nonsteroidal aromatase inhibitor alone in hormone receptor-positive/ERBB2-negative early breast cancer. The absolute improvement in invasive disease-free survival increased from 2.7% at 3 years to 4.9% at 4 years.

METHODOLOGY:

• Cyclin-dependent kinase (CDK) 4 and 6 inhibitors have become the standard of care in advanced breast cancer, with ribociclib being the only one to demonstrate statistically significant progression-free survival and overall survival benefit in first- or second-line treatment. Ribociclib and abemaciclib, also a CDK4/6 inhibitor, have shown statistically significant improvements in invasive disease-free survival in early breast cancer, though with key differences in patient selection, initiation window, dose, and duration.
• Researchers conducted an international, open-label, randomized phase 3 trial analyzing adjuvant treatment for premenopausal and postmenopausal women and men with hormone receptor-positive/ERBB2-negative early breast cancer.
• A total of 5101 patients (median age, 52 years; 99.6% women) with stage IIA (with additional risk factors), IIB, or III disease were randomized 1:1 to receive either ribociclib (400 mg once daily; days 1-21 of 28-day cycle for 36 months) plus nonsteroidal aromatase inhibitor or nonsteroidal aromatase inhibitor alone.
• Primary endpoint was invasive disease-free survival, with secondary endpoints including distant disease-free survival, recurrence-free survival, and overall survival, evaluated using the Kaplan-Meier method.
• Median follow-up duration for invasive disease-free survival was 44.2 months, ranging from 0 to 63 months.

TAKEAWAY:

• Ribociclib plus nonsteroidal aromatase inhibitor demonstrated continued invasive disease-free survival benefit compared with nonsteroidal aromatase inhibitor alone (hazard ratio [HR], 0.72; 95% CI, 0.61-0.84), with 4-year rates of 88.5% vs 83.6%.
• The efficacy benefit remained consistent across subgroups, with distant disease-free survival (HR, 0.72; 95% CI, 0.60-0.85) and recurrence-free survival (HR, 0.70; 95% CI, 0.58-0.83) showing similar improvements.
• Overall survival data, while immature, showed a trend favoring ribociclib plus nonsteroidal aromatase inhibitor compared with nonsteroidal aromatase inhibitor alone (HR, 0.83; 95% CI, 0.64-1.07).
• The safety profile remained stable, with neutropenia (62.8%), arthralgia (38.8%), and nausea (23.5%) being the most common adverse events in the ribociclib plus nonsteroidal aromatase inhibitor arm.

IN PRACTICE:

“This exploratory analysis of the NATALEE randomized clinical trial, with a median follow-up beyond the 3-year treatment duration, demonstrated consistent iDFS [invasive disease-free survival] benefit with ribociclib plus NSAI [nonsteroidal aromatase inhibitor] over NSAI alone,” the authors of the study wrote.

SOURCE:

This study was led by Peter A. Fasching, MD, University Hospital Erlangen in Erlangen, Germany. It was published online on September 25 in JAMA Oncology.

LIMITATIONS:

According to the authors, this is an exploratory analysis of the NATALEE trial and was not powered for formal statistical assessment. The researchers noted that analyses with longer follow-up will be needed to further characterize the long-term impact of adjuvant ribociclib on reducing recurrences.

DISCLOSURES:

This study was supported by Novartis Pharmaceuticals Corporation. Fasching reported receiving personal fees from Novartis during the conduct of this study, as well as grants from Cepheid and personal fees from multiple pharmaceutical companies including Pfizer, Daiichi Sankyo, AstraZeneca, and others outside the submitted work. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.