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Cyclin-dependent kinase 4/6 inhibitors

what have we learnt across studies, therapy situations and substances

Banys-Paluchowski, Malgorzataa; Krawczyk, Nataliab; Paluchowski, Peterc

Current Opinion in Obstetrics and Gynecology: February 2019 - Volume 31 - Issue 1 - p 56–66
doi: 10.1097/GCO.0000000000000511
BREAST CANCER: Edited by Peter A. Fasching

Purpose of review Cyclin-dependent kinases (CDK) are key regulatory enzymes that control cell cycle and cell division. In the recent years, new therapeutic options selectively targeting CDK 4 and 6 have shown promising clinical activity in several solid tumors. Since 2015, three CDK 4/6 inhibitors have been approved for treatment of hormone receptor-positive HER2-negative metastatic breast cancer: palbociclib, ribociclib and abemaciclib. These drugs share a common mechanism of action and have been evaluated in studies with a similar design. The following review gives a clinical overview of the CDK 4/6 inhibitors in breast cancer therapy and highlight current study data with regard to their antitumor efficacy and toxicities.

Recent findings In clinical trials in the first-line and later-line setting, palbociclib, ribociclib and abemaciclib in combination with endocrine therapy significantly prolonged progression-free survival. The most common adverse events during treatment with CDK 4/6 inhibitors are neutropenia, fatigue and gastrointestinal symptoms.

Summary CDK 4/6 inhibitors represent a valuable treatment option for patients with metastatic hormone receptor-positive HER2-negative breast cancer. Although the clinical efficacy of the three agents seems similar, their toxicity profiles differ. Therefore, the choice of a CKD 4/6 inhibitor depends on patient's characteristics and individual preferences.

Video abstract In the video, the author describes the content of the review and present the main topics discussed in the article (

aDepartment of Gynecology and Obstetrics, Asklepios Klinik Barmbek, Hamburg

bDepartment of Obstetrics and Gynecology, Heinrich-Heine-University Düsseldorf, Düsseldorf

cDepartment of Gynecology and Obstetrics, Regio Klinikum Pinneberg, Pinneberg, Germany

Correspondence to Malgorzata Banys-Paluchowski, Department of Gynecology and Obstetrics, Asklepios Klinik Barmbek, Rübenkamp 220, 22307 Hamburg, Germany. E-mail:

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