Evaluation of cyclin-dependent kinase 4/6 inhibitor-induced serum creatinine elevations in patients with hormone receptor positive breast cancer.

Abstract

Background: Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have improved the efficacy of endocrine therapy in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) and are now used in both early-stage and metastatic disease. Recent case reports suggest that pseudo-serum creatinine (Scr) elevations are likely a class effect of CDK4/6i.

Methods: This single-center retrospective analysis included patients aged ≥18 years who received at least one dose of palbociclib, ribociclib, or abemaciclib for the treatment of HR+/HER2- BC in the early or advanced setting. The primary objective was the incidence of pseudo-Scr elevation for each of the three agents. CDK4/6i-induced pseudo-Scr elevation was suspected when the Scr elevation could not be fully attributed to other causes. Secondary endpoints included the grade, onset, duration, and clinical consequences of pseudo-Scr elevation.

Results: 143 patients were included. Pseudo-Scr elevation was suspected in patients treated with palbociclib, ribociclib, or abemaciclib, with incidences of 16% (8/50), 14% (6/43), and 20% (10/50), respectively. Rates did not significantly differ between agents (p = 0.727). Among patients with CDK4/6i-induced pseudo-Scr elevation, all events were grade 1 (8.3%) or 2 (91.7%). The median onset from treatment initiation to first Scr elevation was 33.5, 42, and 21.5 days, for palbociclib, ribociclib, or abemaciclib, respectively.

Conclusion: Pseudo-Scr elevation appears to be a class effect of CDK4/6i, with similar rates of Scr elevation observed across the three agents currently FDA approved.