Insights into the Use of CDK 4/6 Inhibitors in Patients with HR-positive Advanced or Metastatic Breast Cancer

Abstract

Hormone receptor (HR)-positive breast cancer (BC) is the most common subtype of BC and some patients with such tumors experience recurrences. Endocrine-based therapy (ET) (e.g., tamoxifen, aromatase inhibitors (AIs), and fulvestrant) that has improved outcomes in such patients represents the initial therapy for women with HR-positive/human epidermal growth factor receptor 2 (HER2)-negative BC (considering no evidence of visceral crisis). However, the resistance to ET can occur in almost 50% of HR-positive BCs. In order to improve outcomes of patients with HR-positive metastatic BC, new treatment strategies are required. One such therapy is the new class of medications, cyclin-dependent kinase (CDK) 4/6 inhibitors, that have improved the outcomes in such patients (both endocrine-sensitive and endocrine-resistant). This article presents evidence from the main clinical trials, which led to the approval of palbociclib, ribociclib, and abemaciclib. These three CDK 4/6 inhibitors have shown a significant improvement of the progression-free survival (PFS) in patients with HR-positive/HER2-negative metastatic BC when used in combination with selected ETs. In addition, some important patient management considerations, when choosing a particular CDK 4/6 inhibitor for an individual patient are presented. Furthermore, a need to find biomarkers for CDK 4/6 inhibitor sensitivity, efficacy, and resistance, to be able to precisely select the best patient-candidates for this treatment is highlighted.