The FDA's approval of adjuvant ribociclib (Kisqali) in combination with an aromatase inhibitor (AI) on September 17, 2024, marks a significant advancement in the treatment of hormone receptor-positive, HER2-negative (HR+/HER2-) stage II and III early breast cancer. This approval, supported by the phase 3 NATALEE trial, offers a new option for patients at high risk of recurrence, including those with node-negative disease. The NATALEE trial demonstrated a clinically meaningful 25.1% reduction in the risk of disease recurrence (HR, 0.749; 95% CI, 0.628-0.892; P = .0006) compared to endocrine therapy alone. This benefit in invasive disease-free survival (iDFS) was observed across all pre-specified patient subgroups.
Ribociclib vs. Abemaciclib: Navigating Treatment Choices
With ribociclib joining abemaciclib (Verzenio) in the adjuvant setting, clinicians now face the challenge of selecting the most appropriate CDK4/6 inhibitor for individual patients. Abemaciclib is already FDA approved in combination with endocrine therapy for HR+/HER2-, node-positive early breast cancer at high risk of recurrence. The pivotal phase 3 monarchE trial demonstrated a sustained iDFS benefit with abemaciclib plus endocrine therapy over endocrine therapy alone (HR, 0.680; 95% CI, 0.599-0.772; nominal P < .001) at a median follow-up of 54 months.
Dr. Jairam Krishnamurthy, an associate professor at the University of Nebraska Medical Center, emphasized the importance of shared decision-making in an interview with OncLive®. "A lot of shared decision-making will come into play between the patient and the oncologist," he stated, highlighting the need to consider individual patient characteristics and preferences.
Factors Influencing Treatment Selection
When choosing between ribociclib and abemaciclib, several factors come into play. Pre-existing gastrointestinal issues, such as inflammatory bowel disease or diarrhea, may make abemaciclib a less desirable option due to its potential to cause diarrhea. Conversely, patients with pre-existing heart rhythm issues or those taking medications that prolong QT intervals, such as amiodarone, may need to avoid ribociclib, as it can cause QT prolongation.
Dr. Krishnamurthy noted, "We will have to individualize therapy based on patients’ pre-existing conditions. For patients who meet the criteria for both ribociclib and abemaciclib, it’s going to be a question of whether they want to be on a drug for 3 years vs 2 years, and whether they want to be on [abemaciclib], a drug that can potentially cause diarrhea, as opposed to ribociclib, which can cause fatigue and nausea."
Addressing Unmet Needs and Challenges
The approval of adjuvant ribociclib addresses a critical unmet need by providing an additional treatment option to reduce the risk of recurrence in high-risk HR+/HER2- early breast cancer patients. However, challenges remain, including the need to convince patients to adhere to the 3-year treatment duration and the logistical requirements of monthly clinic visits for laboratory tests to monitor for potential adverse effects such as neutropenia and QT prolongation.
