Dr Hurvitz on Sustained Benefit With Adjuvant Ribociclib Plus AI Therapy in HR+/HER2– Breast Cancer

"As patients with hormone receptor–positive early breast cancer experience recurrences years after they have been diagnosed, we can begin in to see that, with an effective drug, the Kaplan Meier curves separate over time."

Sara A. Hurvitz, MD, FACP, medical oncologist, senior vice president and director of—and professor in—the Clinical Research Division, as well as the Smith Family Endowed Chair in Women’s Health at Fred Hutch Cancer Center, discussed 5-year efficacy outcomes from the phase 3 NATALEE trial (NCT03701334) evaliating adjuvant ribociclib (Kisqali) alongside endocrine therapy for patients with early-stage hormone receptor (HR)–positive, HER2-negative breast cancer.

In 2024, the FDA approved adjuvant ribociclib plus an aromatase inhibitor (AI) for the treatment arsenal for patients with HR-positive, HER2-negative early breast cancer at a high risk of recurrence. This regulatory decision was supported by earlier findings from NATALEE, which demonstrated a statistically significant and clinically meaningful improvement in invasive disease-free survival (iDFS) when ribociclib was added to endocrine therapy (n = 2594) compared with endocrine therapy alone (n = 2552).

Data from the 5-year prespecified analysis of NATALEE, presented during the 2025 ESMO Congress, provided confirmation of this durable benefit. Adjuvant ribociclib combined with a nonsteroidal AI continued to show superior iDFS compared with an AI alone, with a hazard ratio of 0.716 (95% CI, 0.618-0.829; 1-sided P < .0001).

The median follow-up for this analysis was 55.4 months. Hurvitz highlighted that the comparison of iDFS rates showed a separation that increased over time, reinforcing ribociclib's effectiveness. Although the 36-month iDFS rates were 90.8% in the ribociclib arm vs 88.0% in the AI-alone arm, the difference widened by 60 months, with rates of 85.5% and 81.0%, respectively.

Hurvitz emphasized that the ongoing separation of the Kaplan Meier curves is crucial because HR-positive early breast cancer patients frequently experience recurrences years after their initial diagnosis. This sustained benefit is particularly exciting compared to earlier presentations, where the difference was less striking. Furthermore, Hurvitz confirmed that throughout this follow-up period, no new safety signals were observed.

References

1. FDA approves Novartis Kisqali to reduce risk of recurrence in people with HR+/HER2- early breast cancer. News release. Novartis. September 17, 2024. Accessed October 19, 2025. https://www.novartis.com/news/media-releases/fda-approves-novartis-kisqali-reduce-risk-recurrence-people-hrher2-early-breast-cancer
2. Crown J, Stroyakovskii D, Yardley D, et al. Adjuvant ribociclib plus nonsteroidal aromatase inhibitor therapy in patients with HR+/HER2– early breast cancer: NATALEE 5-year outcomes. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA14.