Why CDK 4/6 Inhibitors are Practice Changing in Advanced Breast Cancer

Systemic therapy for advanced, hormone receptor-positive (HR+), human epidermal growth factor receptor 2-unamplified (HER2-) breast cancer has drastically evolved over the past several decades, from oophorectomy to combination endocrine and molecularly targeted therapy. Cyclin-dependent kinase (CDK) 4/6 inhibitors are the latest addition to this arsenal of therapies, and while they have been rapidly adopted by most oncologists, many still question whether they belong in the first-line metastatic setting. Recent reporting of overall survival data, however, has re-invigorated the debate and strongly supports first-line use of CDK 4/6 inhibitors. This article will provide an overview of the evolution of systemic therapy in HR+, HER2breast cancer, summarize the data that led to the approval of CDK 4/6 inhibitors, detail the new overall survival data reported in the PALOMA-3, MONALEESA-7, MONALEESA-3, and MONARCH-2 trials, and then discuss why our patients should receive these drugs in the first-line setting for advanced disease.