Nephrotoxicity secondary to CDK 4/6 inhibitors in advanced breast cancer patients and its impact on survival.

Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have become a cornerstone in the treatment of HR+/HER2- advanced breast cancer. While their efficacy is well-established, emerging reports of nephrotoxicity warrant further investigation into its incidence, risk factors, and potential impact on survival outcomes. Objectives: This study aimed to evaluate the incidence and risk factors for nephrotoxicity in patients receiving CDK4/6 inhibitors (palbociclib or ribociclib) and to analyze its association with progression-free survival (PFS) and overall survival (OS). Design: This was a single-center, retrospective cohort study. Methods: We reviewed the medical records of 120 patients with advanced breast cancer treated with palbociclib or ribociclib between October 2018 and July 2024. Nephrotoxicity was defined as a ⩾20% decline in creatinine clearance (CKD-EPI 2021) from baseline. Statistical analyses included descriptive statistics, chi-square tests, t-tests, Kaplan-Meier survival analysis, and Cox regression models. Results: Nephrotoxicity occurred in 28 patients (23.3%). Older age (⩾65 years) and higher baseline urea and creatinine levels were significant risk factors (p < 0.001). Paradoxically, patients who developed nephrotoxicity showed a trend toward better survival outcomes: median PFS was 30 months versus 20 months (p = 0.188), and the 3-year OS rate was 77.9% versus 63.8% (p = 0.801), though these differences were not statistically significant. In multivariate Cox analysis, the development of nephrotoxicity showed a trend toward a 71% reduction in mortality risk (HR = 0.293, p = 0.078), but it was not statistically significant. Conclusion: Nephrotoxicity is relatively common in patients treated with CDK4/6 inhibitors, particularly in older individuals and those with elevated baseline renal parameters. Contrary to conventional expectations, its occurrence may be associated with a trend toward improved survival, possibly reflecting higher drug exposure or effective target inhibition. These findings highlight the need for careful renal monitoring and suggest that nephrotoxicity could serve as a potential surrogate marker for treatment efficacy, warranting validation in larger prospective studies.