Clinician's guide: expert insights on the use of CDK4/6 inhibitors in patients with early breast cancer

The introduction of the cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors abemaciclib and ribociclib to the adjuvant setting marks a significant advancement in the treatment of hormone-receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer (HR+, HER2− EBC). Despite significant strides in early detection and treatment, many patients continue to face the risk of disease recurrence, highlighting the need for more effective adjuvant therapies. These CDK4/6 inhibitors, combined with adjuvant endocrine therapy, have shown promising efficacy in reducing recurrence rates while maintaining a manageable safety profile, as evidenced by the monarchE and NATALEE trials. This paper explores the integration of adjuvant CDK4/6 inhibitors into clinical practice, focusing on disease-free survival and safety outcomes. Key considerations in selecting between abemaciclib and ribociclib are discussed, including patient risk profiles, efficacy and safety profiles, treatment duration, and individual patient preferences. In addition, we discuss managing adverse events to prevent premature discontinuation, with strategies that include dose holds, dose reductions, proactive symptom management, and patient education. The paper also highlights strategies to enhance patient medication adherence and the involvement of multidisciplinary care teams to support treatment delivery. As research continues to evolve, additional follow-ups of the monarchE and NATALEE trials and future trials will further refine patient selection and treatment sequencing, ultimately improving outcomes and enhancing the quality of life for patients with HR+, HER2− EBC.