Management of Adverse Events Due to Cyclin-Dependent Kinase 4/6 Inhibitors

Abstract

Cyclin-dependent kinase (CDK) 4/6 inhibitors have become standard of care in the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer. They have been shown to double the efficacy of endocrine-based treatment. Three oral agents are available to date: palbociclib, ribociclib, and abemaciclib. The aim of this article is to give a short overview of the existing efficacy data, to summarize the recommended clinical monitoring procedures for patients under CDK4/6 inhibitors, and to shed light on the clinical management of the most common treatment-emergent adverse events. The hematological class side effect neutropenia as well as non-hematological toxicities (e.g., impaired liver function, prolonged QTc interval, and diarrhea) are discussed. In addition, the current knowledge about relevant drug interactions is reviewed.

Efficacy and safety of palbociclib in patients with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer with preexisting conditions: A post hoc analysis of PALOMA-2

“…Such findings demonstrate the importance of evaluating the effect of preexisting conditions on drug efficacy and toxicity in patients with cancer. CDK4/6 inhibitors have become the standard of care for patients with HR+/HER2− ABC and have been shown to be generally well tolerated [ 10 ]. However, there is limited information on the effect of these drugs in patients with preexisting conditions.…”

MicroRNA-122-5p inhibits cell proliferation, migration and invasion by targeting CCNG1 in pancreatic ductal adenocarcinoma

“…Cyclin is a kind of cell cycle oscillating protein, which is repeatedly expressed and degraded in the whole cell cycle [27]. Cyclin E, Cyclin D1, Cyclin A and Cyclin B1 occur in G1, late G1 or early S, and the S or G2 phases, respectively [28]. Cyclins function by binding CDKs, which play an important role in cell cycle progression of cancer [29].…”

Transcription and Translation Inhibitors in Cancer Treatment

“…Abemaciclib ( Figure 5) was developed around the same time as palbociclib, and it gained FDA approval in 2017. Even though abemaciclib has similar mechanism of action and usage in cancer treatment for ER positive cancers as palbociclib and ribociclib, the main adverse effects of it are gastro-intestinal issues instead of neutropenia (Chen et al, 2016a;Sledge et al, 2017;Ettl, 2019). This is caused by non-specific inhibition of other kinases in addition to CDK4 and CDK6 and means that abemaciclib can be taken continuously unlike the other CDK4/6 inhibitors (Chen et al, 2016a).…”