The hidden impact of renal impairment on ribociclib exposure and co-medications: a case report.

backgroundRibociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, is widely used in combination with endocrine therapy for advanced hormone receptor-positive breast cancer. However, drug exposure may be highly variable in older patients due to organ dysfunction and polypharmacy, raising the need for therapeutic drug monitoring (TDM). CASE PRESENTATION: We report the case of an 88-year-old woman with metastatic lobular breast carcinoma treated with ribociclib and tamoxifen, who developed progressive renal impairment and was co-prescribed apixaban. Serial TDM demonstrated ribociclib overexposure (Cmin 1022-1318 ng/mL vs. ~ 500 ng/mL expected at steady state), associated with markedly increased plasma concentrations of tamoxifen, endoxifen, and apixaban (923 ng/mL vs. reference peak ~ 206 ng/mL). Monte Carlo simulations incorporating patient covariates confirmed that measured ribociclib concentrations exceeded predicted distributions, likely due to the accumulation of uremic toxins.

conclusionTDM of CDK4/6 inhibitors provides valuable insight into drug exposure in complex geriatric oncology settings. Beyond monitoring ribociclib itself, this approach facilitates a broader discussion on individualized dosing, comedication safety, and management of organ dysfunction in elderly patients with cancer.