A rational approach to dose reduction of CDK4/6 inhibitors in the treatment of patients with advanced breast cancer: A narrative Review

The use of CDK4/6 inhibitors in the treatment of HR⁺/HER2^– breast cancer (BC) has become increasingly widespread in recent years. When assessing the safety of CDK4/6 inhibitors, it was found that during therapy, a significant number of patients require a reduction in the initial dose of the drug due to adverse events (dose reduction), but publications summarizing such data are absent. At the same time, the time to dose reduction and its stages can significantly affect the organization of drug supply for patients with drugs of this group, having an economic and administrative effect on the healthcare system. In this regard, a review of the results of the use of CDK4/6 inhibitors presented in the literature, describing the features of dose reduction, is timely and relevant.

The aim. To conduct a literature review in order to summarize and systematize the results of the use of CDK4/6 inhibitors, describing the features of dose reduction.

Materials and methods. The literature search was carried out in the MedLine (PubMed) and Google Scholar databases from January 2016 to January 2024. The literature search was carried out using the following search queries: “ribociclib OR palbociclib OR abemaciclib” AND “breast cancer and randomized clinical trial”, “CDK4/6 inhibitors OR cyclin-dependent kinase 4/6 inhibitors” AND “metastatic breast cancer” AND “real-world” AND “dose Intensity OR dose reduction”. As a result of the search, 384 publications were found, and 15 publications were included in the final analysis. Data on dose reduction were systematized according to the following criteria: the proportion of patients who underwent the first and, if available, the second reduction, the time to dose reduction, and the intensity of dosing.

Results. Analysis of data from randomized clinical trials showed that a dose reduction was required in 31.8–57.4% of patients using CDK4/6 inhibitors. At the same time, the second dose reduction was carried out in 17.4–40% of patients. The median time to the first stage of reduction ranged from 1.2 to 3.2 months. The median relative dose intensity ranged from 66.3 to 93.0%. According to the results of the analysis of real clinical practice data, dose reduction was carried out in 28.1–59.1% of patients. At the same time, the first stage of reduction was carried out at 1–3 months of therapy, and the second at 4–17 months from the start of treatment.

Conclusion. A literature review was conducted to systematize the results of the use of CDK4/6 inhibitors, describing the features of dose reduction. Approximately up to 60% of patients need a dose reduction, regardless of the selected CDK4/6 inhibitor. Data on the frequency and time to dose reduction vary; therefore, the need for reduction in an individual patient may arise at any time, which may complicate the process of planning the provision of anti-tumor therapy drugs.

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