The role of CDK4/6 inhibitors in early breast cancer.

The use of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) has proven to be a successful strategy in the treatment of advanced hormone receptor-positive (HR ⁺ ) and human epidermal growth factor receptor 2-negative (HER2 ^- ) breast cancer (BC), leading to a strong interest in their possible role in the treatment of early luminal BC. In this review we collect the most relevant and recent information on the use of CDK4/6i for the treatment of early BC in the neoadjuvant and adjuvant settings. Specifically, we evaluate the results of the large phase 3 adjuvant trials recently released, which have yielded apparently divergent results. We also examine the relevance of biomarkers as response predictive factors for CDI4/6i, the combination between radiotherapy and CDK4/6i, and provide a critical discussion on the evidence that we have so far and future directions of the role of these drugs in the treatment of early BC.
Competing Interests: Declaration of competing interest MGG reports consulting fees and honoraria from Pfizer, Agendia, and Kern; advisory roles for AstraZeneca and Daiichi-Sankyo; travel grants from Pfizer, Roche, Novartis, and Kern. EA reports advisory roles for Roche, Novartis, Pfizer, Eli Lilly, BMS, AstraZeneca, Genomic Health, and Nanostring; travel grants from Celgene; research grants from Roche, Pfizer, Sysmex, MSD, and Nanostring. JG reports consulting fees and honoraria from Novartis, Pfizer, AstraZeneca and Daiichi-Sankyo; advisory roles for Novartis, Pfizer, Eli Lilly and AstraZeneca. JdlH-R reports consulting fees and honoraria from Pfizer, Novartis, and Agendia; advisory roles for AstraZeneca, Daiichi-Sankyo, Pfizer, Novartis and Roche; travel grants from Astra Zeneca, Pfizer, Roche and Novartis. EC reports consulting fees from Pfizer, Eli Lilly, Roche, Novartis, AstraZeneca and MSD; participating as a speaker for Roche, Pfizer and Eli Lilly; travel grants from Roche and Pfizer. PT reports personal fees from AstraZeneca and honoraria for participation in advisory boards from Amgen, AstraZeneca, MSD, Roche, Pfizer and Eisai. DC is an employee of and may own stock in Pfizer Inc. AL-C reports owing stock, patents and intellectual property with MedSIR; consultant for AstraZeneca, Daiichi-Sanyo, MSD, Novartis, Pfizer, Roche and Eli Lilly; research funding from Eisai, Daiichi-Sanyo, Roche, Pfizer, Eli Lilly, MSD, Genomic-Health, Agendia and Pierre Fabre; travel grants from Roche, Pfizer and Eli Lilly; providing expert testimony for AstraZeneca.
(Copyright © 2021. Published by Elsevier Ltd.)