Dr Advani on the Evaluation of Ribociclib/Endocrine Therapy in HR+/HER2– Breast Cancer

Pooja Advani, MBBS, MD, hematologist/oncologist, Mayo Clinic Comprehensive Cancer Center, discusses the evaluation of ribociclib (Kisqali) plus endocrine therapy for the adjuvant treatment of patients with hormone receptor (HR)–positive/HER2-negative breast cancer.

The phase 3 multicenter, randomized, open-label NATALEE trial (NCT03701334) evaluated the efficacy and safety of ribociclib in combination with endocrine therapy in this patient population. The NATALEE enrollment criteria broadened the pool of patients with high-risk, estrogen receptor–positive, HER2-negative early breast cancer who are eligible to receive CDK4/6 inhibitors plus endocrine therapy to enhance their survival prospects, Advani begins. Unlike the phase 3 monarchE trial (NCT03155997) of endocrine therapy with or without abemaciclib (Verzenio), which only enrolled patients with high-risk disease, the NATALEE trial also included high-risk patients with stage II disease, she explains. Another point of contrast between the 2 studies was the dosage of ribociclib administered, which was lower in NATALEE than that used in the metastatic setting—400 mg instead of 600 mg, Advani notes.

Additionally, in NATALEE, ribociclib treatment spanned 3 years compared with the standard 2-year duration of abemaciclib treatment, she expands. Despite these unique characteristics, the NATALEE trial successfully achieved its primary end point: improvement in invasive disease-free survival (IDFS) with adjuvant ribociclib combined with a non-steroidal aromatase inhibitor (NSAI) vs an NSAI alone. However, the overall survival data from NATALEE are premature as most patients have yet to complete the prespecified 3-year ribociclib regimen, she elucidates. Ribociclib is currently pending FDA approval for patients with HR-positive/HER2-negative breast cancer, and thus cannot be currently used in the clinic, Advani says, adding that the absolute IDFS benefit with ribociclib in the current analysis was 3.3%, which raises questions about the clinical significance of this agent. Furthermore, the occurrence of grade 3 or higher liver adverse effects in 8.3% of patients who received ribociclib plus an NSAI warrants careful consideration, she reports.

If the NATALEE regimen receives FDA approval for patients with HR-positive/HER2-negative breast cancer, providing another CDK4/6 inhibitor treatment option, patients meeting monarchE enrollment criteria should receive the monarchE regimen because the monarchE data have longer follow-up compared with those from NATALEE. For patients not meeting monarchE criteria or those intolerant to abemaciclib, ribociclib could be considered, particularly for those with high-risk disease, Advani concludes.