FDA Approves Ribociclib in Combination With an Aromatase Inhibitor for HR+/HER2- Early Breast Cancer

Ribociclib (Kisqali; Novartis) in combination with an aromatase inhibitor (AI) received FDA approval for the adjuvant treatment of patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) stage 2 and 3 early breast cancer (EBC) at high risk of recurrence. The decision is based on data from the phase 3 NATALEE trial (NCT03701334) which demonstrated a clinically meaningful reduction in risk of disease recurrence and well-tolerated safety.The data were presented at the European Society for Medical Oncology 2024 congress.¹

The treatment significantly reduced risk of occurrence by 25% compared with endocrine therapy alone. Image Credit: © Jack - stock.adobe.com

According to the American Cancer Society, more than 300,000 women will be diagnosed with breast cancer (BC) in 2024 in the US, accounting for approximately 42,000 deaths. HR+/HER2- is the most common subtype of BC, accounting for nearly 70% of all new cases. Patients with HR+/HER2– BC are at high risk of their cancer returning—typically as incurable metastatic disease, highlighting the need for efficacious treatments that overcome disease recurrence.^2-4

Ribociclib is a selective cyclin-dependent kinase inhibitor that targets cyclin-dependent kinase 4 and 6 (CDK4/6). When overactivated, these proteins can encourage the rapid growth and proliferation of cancer cells, ensuring they do not continue to replicate. Ribociclib is an orally administered tablet taken for 3 weeks followed by 1 week off the treatment, in combination with 4 weeks of any AI. In the NATALEE trial, the 400 mg dosage (2 200 mg tablets) demonstrated favorable safety and was well-tolerated.⁴

The global phase 3 multi-center, open-label trial included more than 1500 adults with HR+/HER2- EBC across 20 countries who were randomized to receive ribociclib in combination with ET as an investigational adjuvant treatment versus ET monotherapy. The adjuvant ET in both treatment arms was a non-steroidal AI (NSAI; anastrozole or letrozole) and goserelin, if applicable. The primary end point of the trial was invasive disease-free survival benefit as defined by the Standardized Definitions for Efficacy End Points (STEEP) criteria.⁴

The data showed a 25.1% (HR=0.749; 95% CI: 0.628, 0.892; P=0.0006) reduction in risk of disease recurrence in patients receiving ribociclib and ET compared with ET alone, including those with high-risk node-negative (N0) disease. Additionally, researchers observed a deepening benefit beyond 3 years and a 28.5% risk of recurrence (HR=0.715; CI 95% 0.609-0.840; P<.0001).⁴

"The FDA approval of Kisqali for this early breast cancer population, including those with N0 disease, is a pivotal moment in improving our approach to care," Dennis J. Slamon, MD, director of clinical/translational research at UCLA Jonsson Comprehensive Cancer Center, chairman of the Board of Translational Research in Oncology (TRIO), and NATALEE trial lead investigator. "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."⁴

REFERENCES

1. A trial to evaluate efficacy and safety of ribociclib with endocrine therapy as adjuvant treatment in patients with hr+/​her2- early breast cancer (natalee). ClinicalTrials.gov Identifier: NCT03701334. Updated October 3, 2023. Accessed September 17, 2024. https://clinicaltrials.gov/study/NCT03701334

2. Key statistics for breast cancer. American Cancer Society. January 17, 2024. Accessed September 17, 2024. https://www.cancer.org/cancer/types/breast-cancer/about/how-common-is-breast-cancer.html

3. Pharmacists enhance care for patients with hr+/her2– breast cancer on cdk4/6 inhibitor therapy. Pharmacy Times. August 28, 2024. Accessed September 17, 2024. https://www.pharmacytimes.com/view/pharmacists-enhance-care-for-patients-with-hr-her2-breast-cancer-on-cdk4-6-inhibitor-therapy

4. FDA approves Novartis Kisqali® to reduce risk of recurrence in people with HR+/HER2- early breast cancer. Novartis. September 17, 2024. Accessed September 17, 2024. https://www.novartis.com/us-en/news/media-releases/fda-approves-novartis-kisqali-reduce-risk-recurrence-people-hrher2-early-breast-cancer