CDK 4/6 inhibitors

CDK4/6 inhibitors are a class of drugs that target particular enzymes, called CDK4 and CDK6. CDK stands for cyclin-dependent kinase, and it is an enzyme that is important for cell division. CDK4/6 inhibitors interrupt signals that stimulate the proliferation of malignant (cancerous) cells.

Certain cancers, for example, hormone receptor-positive breast cancer, are more likely to have disturbances in CDK4/6, and CDK 4/6 inhibitors may form part of the treatment protocol. Most often, CDK4/6 inhibitors are given synergistically with hormonal therapy (such as an aromatase inhibitor or fulvestrant), although the CDK4/6 inhibitor abemaciclib may be used alone to treat hormone receptor-positive, HER2-negative metastatic breast cancer in pre-treated patients.

Research shows CDK4/6 inhibitors increase the time people have before cancer spreads (progression-free survival). Piezzo (2020) also showed a significant improvement in overall survival (OS) for CDK 4/6 inhibitors as a group for both aromatase inhibitor (AI)-sensitive (HR 0.75, 95% CI) and AI-resistant patients (HR 0.77, 95% CI [0.67–0.89]). However, single-drug analysis revealed palbociclib was the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68–1.02]).

Common side effects include fatigue and gastrointestinal disturbances, such as nausea, diarrhea, and vomiting. Bone marrow suppression resulting in neutropenia and leukopenia may also occur, although anemia and thrombocytopenia are less common. In general, the side effects associated with CDK4/6 inhibitor therapy are less severe than those experienced with chemotherapy.

1. Piezzo, M., Chiodini, P., Riemma, M., Cocco, S., Caputo, R., Cianniello, D., Di Gioia, G., Di Lauro, V., Rella, F. D., Fusco, G., Iodice, G., Nuzzo, F., Pacilio, C., Pensabene, M., & De Laurentiis, M. (2020). Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis. International journal of molecular sciences, 21(17), 6400. https://doi.org/10.3390/ijms21176400