Ribociclib plus fulvestrant in the treatment of breast cancer.

INTRODUCTION: Endocrine therapy (ET) is a standard first-line treatment for hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC) Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have demonstrated significantly improved progression-free survival (PFS) with ET in patients with ABC. Recent reports indicate that the addition of the CDK4/6i ribociclib to ET, including fulvestrant, significantly improves PFS and overall survival (OS). AREAS COVERED: This review summarizes the efficacy and safety of ribociclib plus fulvestrant in HR+/HER2- ABC and its role in clinical practice. Various post-progression strategies are discussed. EXPERT OPINION: In MONALEESA-3, ribociclib +fulvestrant significantly improved PFS and OS in postmenopausal patients who received no prior chemotherapy and ≤1 prior line of ET for ABC and benefited many patient subgroups, including those with visceral metastases and ET resistance. The safety of this combination is manageable and consistent with the known safety profile of ribociclib, with myelosuppression being a common and expected toxicity; other relevant toxicities requiring monitoring that occur at a low rate include hepatobiliary toxicity, pneumonitis, and QTc prolongation. There is an important role for CDK4/6i + ET, including ribociclib + fulvestrant, in clinical practice. The optimal position of CDK4/6i in first or subsequent lines of treatment and the optimal post-CDK4/6i progression strategies are not yet elucidated.