FDA Approves Ribociclib With an Aromatase Inhibitor in Early Breast Cancer

• The FDA has approved adjuvant ribociclib (Kisqali) plus an aromatase inhibitor (AI) in hormone receptor (HR)-positive, HER2-negative stage II and III early breast cancer at high risk of recurrence.
• This indication includes patients with node-negative disease.
• Data from the phase 3 NATALEE trial (NCT03701334) support this approval as the combination led to an improvement in invasive disease-free survival (iDFS) vs endocrine therapy alone in this patient population.

Adjuvant ribociclib plus an AI has been approved by the FDA for the treatment of patients with HR-positive, HER2-negative stage II and III early breast cancer at a high risk of recurrence.^1,2

Findings from the phase 3 NATALEE trial, a multicenter, randomized, open-label, phase 3 study assessing the combination in adult patients with HR-positive/HER2-negative early breast cancer, support this approval. Once enrolled in the study, patients were given ribociclib at a dose of 400 mg daily in a 3-weeks-on-1-week-off manner for 3 years.

The combination led to a statistically significant and clinically meaningful improvement in iDFS when used for the treatment of patients with HR-positive, HER2-negative early breast cancer vs endocrine therapy alone.

"The FDA approval of [ribociclib] for this early breast cancer population, including those with [node-negative] disease, is a pivotal moment in improving our approach to care," Dennis J. Slamon, MD, director of clinical/translational research, UCLA Jonsson Comprehensive Cancer Center and chairman of the Board of Translational Research In Oncology and NATALEE trial lead investigator, said in a news release.2 "Today's approval allows us to offer treatment with a CDK4/6 inhibitor to a significantly broader group of people as a powerful tool that, combined with endocrine therapy, can help further minimize their risk of cancer returning."

At the 2023 ASCO Annual Meeting, data from the second interim analysis of the study were presented. Here, it was shown that among patients who received the combination (n = 2549), there was a 3-year iDFS rate of 90.4% compared with 87.1% in patients who received endocrine therapy alone (n = 2552; HR, 0.748; 95% CI, 0.618-0.906; P =.0014). The median follow-up for iDFS was 27.7 months. This benefit was consistent across patient subgroups, regardless of disease stage, menopausal status, or nodal status.³

“The key findings are that we're able to reduce the invasive disease-free recurrences by 25%. We're able to reduce metastatic distant metastatic disease by 26%,” Slamon told Targeted Oncology^TM in a prior interview.

Moreover, findings from an exploratory analysis of the study were recently presented at the 2024 ESMO Congress. This was performed with an additional 10.9 months of follow-up and showed that at a median follow-up of 44.2 months, the 3-year iDFS rates were 90.8% with ribociclib plus an AI compared with 88.1% with an AI alone in the intention-to-treat population. The respective iDFS rates at 4 years were 88.5% vs 83.6% (HR, 0.715; 95% CI, 0.609-0.840; P <.0001).⁴

Notably, most iDFS events in each arm were linked with distant recurrence (6.9% vs 9.6%). The iDFS benefit with the ribociclib-based combination also extended across all key prespecified subgroups based on characteristics such as menopausal status, prior chemotherapy, region, and prior endocrine therapy.

In addition to this approval, the FDA also approved the ribociclib and letrozole co-pack for the same indication.¹

REFERENCES:

1. FDA approves Kisqali with an aromatase inhibitor and Kisqali Femara Co-Pack for early high-risk breast cancer. News release. FDA. September 17, 2024. Accessed September 17, 2024. https://tinyurl.com/njts3tvy

2. FDA approves Novartis Kisqali® to reduce risk of recurrence in people with HR+/HER2- early breast cancer. News release. Novartis. September 17, 2024. Accessed September 17, 2024. https://tinyurl.com/5n8d6mne

3. Slamon DJ, Stroyakovskiy D, Yardley DA, et al. Ribociclib and endocrine therapy as adjuvant treatment in patients with HR+/HER2- early breast cancer: primary results from the phase III NATALEE trial. J Clin Oncol. 2023;41(suppl 17):LBA500. doi:10.1200/JCO.2023.41.17_suppl.LBA500

4. Fasching PA, Stroyakovskiy D, Yardley DA, et al. Adjuvant ribociclib plus nonsteroidal aromatase inhibitor in patients with HR+/HER2– early breast cancer: 4-year outcomes from the NATALEE trial. Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. LBA13.