NATALEE Data Show Ribociclib Reduces Risk of Recurrence for High-Risk Node-Negative Early Breast Cancer

In a subgroup analysis of the phase 3 NATALEE trial, the addition of ribociclib (Kisqali; Novartis) to endocrine therapy (ET) showed a 28% risk reduction in invasive disease-free survival (iDFS) in patients with high-risk, node-negative (N0) hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC). Trial investigators observed that in this high-risk patient supgroup, ribociclib plus ET, compared to ET alone, improved rates of iDFS, distant recurrence-free survival (DRFS), and distant disease-free survival (DDFS).¹

NATALEE trial investigators observed that in this high-risk patient supgroup, ribociclib plus ET, compared to ET alone, improved rates of iDFS, DRFS, and DDFS. Image Credit: © Sebastian Kaulitzki - stock.adobe.com

In an interview with Pharmacy Times, Aimee Keegan, PharmD, BCOP, clinical pharmacist specialist, medical oncology lead at City of Hope, commented on the NATALEE trial results, noting that the rates of iDFS at 3 years showed a significant difference in ribociclib plus non-steroidal aromatase inhibitor (anastrozole [Arimidex; AstraZeneca] or letrozole [Femara; Novartis]) vs ET alone.²

“Specifically looking at stage 2 vs stage 3 patients, they found that ribocilib led to a 30% risk in reduction for stage 2 patients and a 24.5% risk reduction for stage 3 patients,” Keegan said. “Unfortunately, the overall survival data is still immature at this time, so this has not yet led to any kind of approval or the addition of ribociclib to the [National Comprehensive Cancer Network] guidelines, so this is still very early information that we have.”²

The NATALEE trial data presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, were noted to be consistent with the significant benefits observed in the broad population of patients with stage 2 and 3 HR+/HER2- EBC, which were data initially presented at ASCO 2023. Specifically, 3-year iDFS rate in the ribocilib plus ET arm was 93.2%, while ET alone was 90.6% (HR=0.72; 95% CI: 0.41, 1.27). Further, 3-year DRFS rate was 96.3% and 92.5% (HR=0.58; 95% CI: 0.29, 1.17), respectively, and 3-year DDFS rate was 94.3% and 91.5% (HR=0.70; 95% CI: 0.38, 1.29), respectively.¹

“More than 1 in 3 patients diagnosed with [EBC], regardless of nodal involvement, are at risk of experiencing recurrent disease despite treatment with standard chemotherapy and/or [ET],” said NATALEE trial principal investigator Denise A. Yardley, MD, associate director, Breast Cancer Research and executive member, Breast Cancer Research Executive Committee, Sarah Cannon Research Institute, in a press release. “Notably, the NATALEE trial has shed light on the [N0] patient population, an important at-risk subgroup that could benefit from more options to reduce their risk of their cancer returning. The findings from this trial underscore the efficacy of ribociclib in early-stage [N0] breast cancer, highlighting its role as a viable and well-tolerated treatment intervention that could significantly diminish the recurrence risk for this particular group.”¹

Furthermore, updated trial data at 2024 ASCO showed that the safety profile of ribociclib at 400 mg in the high-risk, N0 subgroup was consistent with the well-tolerated profile previously observed in the intent-to-treat population. Specifically, adverse events (AEs) were generally low-grade, and in the N0 subgroup, the rate of discontinuation due to all grade AEs was 24% vs 8% with ribociclib plus ET vs ET alone. Additionally, no new safety signals were identified.¹

“Currently available targeted therapies are approved only for a small proportion of patients, leaving a large number of people diagnosed with HR+/HER2- early breast cancer at risk of cancer returning, particularly those with high-risk N0 tumors,” said Jeff Legos, executive vice president, Global Head of Oncology Development, Novartis, in the press release. “Our robust body of data continues to support the potential for [ribociclib] to benefit many more patients as they seek to reduce the likelihood of their cancer coming back with the addition of a CDK4/6 inhibitor to their [ET].”¹

These NATALEE trial data were submitted to the FDA and European Medicines Agency in 2023, with Novartis noting in the press release that further submissions to global authorities will be ongoing.¹

REFERENCES

1. Latest analysis of Novartis NATALEE study shows Kisqali® reduces risk of cancer recurrence for early breast cancer patients with high-risk node-negative disease. Novartis; May 31, 2024. Accessed June 1, 2024. https://www.novartis.com/us-en/news/media-releases/latest-analysis-novartis-natalee-study-shows-kisqali-reduces-risk-cancer-recurrence-early-breast-cancer-patients-high-risk-node-negative-disease
2. NATALEE: Ribociclib and Endocrine Therapy in HR+/HER2- Early Breast Cancer. Pharmacy Times. April 24, 2024. Accessed June 1, 2024. https://www.pharmacytimes.com/view/natalee-ribociclib-and-endocrine-therapy-in-hr-her2--early-breast-cancer