What is the comparison between Ribociclib (Kisqali) and MonarchE trials?

From the Guidelines

The NATALEE trial demonstrated a 3.3% improvement in invasive disease-free survival with the addition of ribociclib to adjuvant endocrine therapy, whereas the MonarchE trial showed a 6.4% reduction in the absolute risk of recurrence at 4 years with the addition of abemaciclib to endocrine therapy in patients with HR-positive/HER2-negative, high-risk breast cancer. The key difference between the two trials is the patient population and the CDK4/6 inhibitor used. The NATALEE trial evaluated ribociclib in patients with stage II and stage III HR-positive, HER2-negative breast cancer, while the MonarchE trial evaluated abemaciclib in patients with HR-positive/HER2-negative, high-risk breast cancer, defined as 4 or more pathologically involved lymph nodes confirmed preoperatively and/or at surgery, or 1 to 3 pathologically involved lymph nodes with additional high-risk features 1.

• The NATALEE trial used a lower dose of ribociclib (400 mg daily) for a longer duration (3 years), and showed a statistically significant improvement in invasive disease-free survival (HR, 0.75; 95% CI, 0.62–0.91; P = .003) 1.
• In contrast, the MonarchE trial used abemaciclib for 2 years and demonstrated a significant reduction in the absolute risk of recurrence at 4 years (HR, 0.664; 95% CI, 0.578–0.762; P < .0001) 1.
• The ASCO guideline rapid recommendation update favors using abemaciclib over ribociclib in patients who meet criteria for both monarchE and NATALEE, due to abemaciclib's longer follow-up, deepening benefit over time, and shorter duration of therapy 1.
• However, the choice between ribociclib and abemaciclib should be individualized, considering the benefits, risks, costs, and preferences for each patient 1.

The current guidelines recommend considering 2 years of adjuvant CDK 4/6 therapy with abemaciclib in combination with endocrine therapy in patients with HR-positive/HER2-negative, high-risk breast cancer, as a category 1, preferred option for this setting 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Comparison of Ribociclib (Kisqali) and MonarchE Trials

• The MonarchE trial evaluated the efficacy and safety of abemaciclib plus endocrine therapy versus endocrine therapy alone in patients with HR+/HER2- early breast cancer 2.
• In contrast, the NATALEE trial assessed the efficacy and safety of adjuvant ribociclib plus endocrine therapy versus endocrine therapy alone in patients with HR+/HER2- early nonmetastatic breast cancer 3.
• Both trials demonstrated improved disease-free survival (DFS) with the addition of CDK4/6 inhibitors to endocrine therapy, with the MonarchE trial showing a 5-year DFS of 77% in abemaciclib-eligible patients and the NATALEE trial showing a 5-year DFS of 86% in ribociclib-eligible patients 2.
• The patient populations in the two trials differed, with the MonarchE trial including patients with ≥4 axillary nodes involved or 1-3 nodes plus primary >5 cm or grade 3, and the NATALEE trial including patients with node-positive and node-negative disease with primary >5 cm or >2 cm grade 3 2.
• The treatment duration and dosage of the CDK4/6 inhibitors also varied between the two trials, with the NATALEE trial using a reduced dose of ribociclib (400 mg/day) for a longer duration (36 months) compared to other adjuvant CDK4/6 inhibitor trials 3.

Efficacy and Safety of Ribociclib

• Ribociclib has demonstrated improved progression-free survival (PFS) and overall survival (OS) in combination with endocrine therapy in patients with HR+/HER2- advanced breast cancer 4, 5.
• The MONALEESA-3 trial showed that ribociclib in combination with fulvestrant improved PFS and OS in postmenopausal women with metastatic HR+/HER2- breast cancer 4.
• Ribociclib has a higher incidence of liver function test abnormalities and QTc prolongation compared to other CDK4/6 inhibitors, and may be contraindicated in patients with cardiac morbidities or other risk factors for QTc prolongation 4.

Real-World Analysis of Breast Cancer Patients

• A real-world analysis of breast cancer patients found that 17.5% of patients were eligible for abemaciclib and 41.3% were eligible for ribociclib based on clinical trial criteria 2.
• The analysis showed that the 5-year DFS was lower in patients eligible for abemaciclib or ribociclib compared to those not eligible, highlighting the potential benefit of CDK4/6 inhibitors in high-risk patients 2.