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Review
. 2023 Dec;50(6):131-139.
doi: 10.1053/j.seminoncol.2024.01.002. Epub 2024 Jan 13.

CDK4/6 inhibitors in the treatment of metastatic breast cancer: Focus on toxicity and safety

Demi Wekking  1 , Matteo Lambertini  2 , Mariele Dessì  3 , Nerina Denaro  4 , Fabio Bardanzellu  5 , Ornella Garrone  4 , Mario Scartozzi  6 , Cinzia Solinas  3
Affiliations
Free article
Review

CDK4/6 inhibitors in the treatment of metastatic breast cancer: Focus on toxicity and safety

Demi Wekking et al. Semin Oncol. 2023 Dec.
Free article

Abstract

The development of oral cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors, including palbociclib, ribociclib, and abemaciclib, has revolutionized the treatment landscape for patients with hormone-receptor-positive (HR+) and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (BC). When combined with an aromatase inhibitor or fulvestrant, these agents have been approved as first-line therapy in the metastatic setting. Abemaciclib has also gained FDA approval for patients with HR-positive, HER2-negative, node-positive, early BC at high risk of recurrence. Moreover, ribociclib has recently improved disease-free survival in patients with stage II or III HR+/HER2-negative early BC. CDK4/6 inhibitors have favorable safety profiles. However, the available agents have different toxicity profiles that must be clearly discussed with the patients for optimal clinical decisions. This manuscript aims to review CDK4/6 inhibitor-related treatment-associated adverse events, identify risk factors for intolerable adverse events, and assess their safety in special patient populations such as the elderly and those with renal insufficiency. Enhanced knowledge and understanding of CDK4/6 inhibitor-related toxicities can improve treatment strategies and ultimately enhance patient care.

Keywords: Breast cancer; CDK4/6 inhibitors; Risk factors; Safety management; Toxicity profiles.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Matteo Lambertini reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD and Exact Sciences and speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Knight and Takeda, Travel Grants from Gilead and Daiichi Sankyo, and research support (to the Institution) from Gilead outside the submitted work. Cinzia Solinas received travel grants from Ipsen and Lilly outside the submitted work. Nerina Denaro report: support for attending meetings and/or travel from Merck, msd, Novartis, and pierre fabre. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bms, msd, and merck Ornella Gerrone report: consulting fees from EISAI, Daiichi-Sankyo, Astra Zeneca, Gilead, and Seagen. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer, Novartis, Lilly and MSD. Support for attending meetings and/or travel from Novartis, Daiichi-Sankyo, and Ipsen. Mario Scartozzi reports: consulting fees from MERCK, MSD, SERVIER, AMGEN, and GILEAD. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from MERCK, MSD, SERVIER, and EISAI. Support for attending meetings and/or travel from MERCK. Participation on a Data Safety Monitoring Board or Advisory Board for ROTTAPHARM BIOTECH. All other authors have no conflict of interest to declare related to the present topic.

References