(091) Evaluation of Cyclin-Dependent Kinase 4/6 Inhibitor-Induced Serum Creatinine Elevations

Poster Abstract: The first-line treatment for hormone receptor (HR)-positive, human epidermal growth factor receptor (HER2)-negative metastatic breast cancer consists of a combination of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors (palbociclib, ribociclib, or abemaciclib) plus endocrine therapy (ET). The MONARCH trials revealed that 98.3% of patients who received abemaciclib experienced an increase serum creatinine (Scr) level. In vitro and in vivo data suggest that abemaciclib can cause a pseudo-elevation in Scr levels by inhibiting renal tubular secretion transporters. No Scr elevations were reported with palbociclib in the phase III PALOMA-2 trial, nor with ribociclib in the phase III MOSALEESA studies. However, recent case reports have raised concerns that pseudo-Scr elevations may be a class effect of CDK 4/6 inhibitors. More research is needed to understand the incidence, patterns, and potential consequences of Scr elevations in breast cancer patients treated with CDK4/6 inhibitors. The primary objective was to evaluate the incidence of pseudo-Scr elevation in breast cancer patients who received CDK4/6 inhibitors. Scr elevation was defined and graded according to Common Terminology Criteria for Adverse Events Version 5 criteria. Secondary endpoints included the grade, onset, duration, time to recovery to baseline, and clinical consequences of pseudo-Scr elevation. This single-center retrospective analysis included patients ≥18 years of age who received one or more doses of palbociclib, ribociclib, or abemaciclib for the treatment of HR-positive early or metastatic breast cancer from 1 January 2015 through 31 August 2023. Exclusion criteria were active treatment for another malignancy, concomitant biological agents and/or immunotherapy, history of prescription of more than one CDK4/6 inhibitor, and receipt of a CDK4/6 inhibitor on a clinical trial protocol. Patients were categorized into three groups based on the CDK4/6 inhibitor received. Data collection included baseline demographic information, cancer diagnosis, CDK4/6 inhibitor treatment details (dose, date of treatment initiation, interruption, and cessation), Scr levels from prior to start of therapy until study period cutoff or 3 months after cessation, and, if any, interventions needed for Scr elevation. Incidences of pseudo-Scr elevations between the three groups were compared using the Chi-squared test. Descriptive statistics were used for patient characteristics and secondary endpoints. Overall, 144 patients were identified. The incidence of Scr elevation for palbociclib, ribociclib, and abemaciclib were 17.6%, 25.6%, and 26%, respectively. Final statistical analyses and secondary endpoints are pending and will be presented with the research poster. Conclusions are pending.

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