![]() Ribociclib is an orally bioavailable, selective CDK4/6 inhibitor that has demonstrated efficacy in HR+, HER2– metastatic breast cancer when used in combination with a nonsteroidal aromatase inhibitor (AI) or fulvestrant. Overexpression of the CCND1 oncogene, which occurs in as many as 50% of breast cancers, leads to cell cycle dysregulation and cancer cell survival, and is thought to be a mechanism of endocrine resistance ( Ribnikar et al., 2019). Furthermore, there is a close link between cyclin D (CCND1) and estrogen receptor–mediated transcription. ![]() Once inactivated, Rb releases the transcription factor E2F, which promotes progression from the G1 to S phase of the cell cycle, allowing for DNA replication and tumor progression. Specifically, cyclin D binds to CDK4/6, which results in phosphorylation of Rb, leaving the tumor suppressor gene inactive. The cell cycle is regulated by several proteins, including the cyclin-dependent kinase-retinoblastoma (Rb) signaling pathway. The contents of this article will focus on the mechanism of action, efficacy and safety data, dosing, monitoring, and practical implications of these agents. The purpose of this article is to provide the advanced practitioner with the tools necessary to manage metastatic HR+, HER2– breast cancer patients initiating therapy with ribociclib or abemaciclib. Food & Drug Administration (FDA) approval in February 2015 however, this article will focus on the newer CDK4/6 inhibitors, ribociclib and abemaciclib, which gained FDA approval in March 2017 and February 2018, respectively. Palbociclib was the first CDK4/6 inhibitor to receive U.S. The addition of the cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio) to standard endocrine therapy has significantly improved progression-free survival (PFS) as initial and second-line therapy in patients with HR+, human epidermal growth factor receptor 2–negative (HER2–) metastatic breast cancer ( D’Souza et al., 2018). ![]() In the past decade, research has focused on the development of novel drug targets that aim to restore or extend endocrine sensitivity ( D’Souza, Spicer, & Lu, 2018). Approximately 75% of breast cancers are considered hormone receptor–positive (HR+) and express estrogen and/or progesterone receptors ( Anderson, Chatterjee, Ershler, & Brawley, 2002), with endocrine therapy serving as the mainstay of systemic treatment ( Ribnikar, Volovat, & Cardoso, 2019).ĭespite the widespread use of endocrine therapy, a proportion of patients will develop endocrine resistance, leading to treatment failure and progressive disease. Although the development of newer therapies and better screening methods has increased breast cancer survival rates, metastatic disease is still the second most common cause of cancer-related death in women ( Siegel et al., 2020). ![]() It is estimated that 279,100 people were diagnosed with breast cancer in 2020. Breast cancer is the most commonly diagnosed cancer in the United States, accounting for 30% of all new cancer diagnoses annually. ![]()
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