Evaluation of cyclin-dependent kinase 4/6 inhibitor-induced serum creatinine elevations in patients with hormone receptor positive breast cancer.
Authors: Emily Ly, Frederick Matthew Howard, Nan Chen, Olwen Mary Hahn, Gini F. Fleming, Rita Nanda, Shivani Patel, Lida Thimothy, Heng Yang
Journal: Journal of Clinical Oncology (2024)

e23304 Background: Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have improved the efficacy of endocrine therapy in hormone receptor-positive (HR+)/HER2- breast cancer (BC) and are now used in both early-stage and metastatic disease. In the MONARCH-3 trial, 98% of patients (pts) treated with abemaciclib (abema) experienced elevated serum creatinine (sCr). Chappell et al. reported that abema caused pseudo-elevation in sCr by inhibiting renal tubular secretion. This effect was not evaluated in trials of palbociclib (palbo) and ribociclib (ribo), but case reports suggest that pseudo-sCr elevations are likely a class effect of CDK 4/6i. In this retrospective study, we sought to evaluate the incidence of sCr elevation in pts being treated with CDK4/6i for early and advanced stage BC. Methods: This single-center retrospective analysis included pts aged ≥18 years who received at least one dose of palbo, ribo, or abema for the treatment (tx) of HR+/HER2- BC in the early or advanced setting at the University of Chicago Medicine from January 2015 to August 2023. Pts were categorized into subgroups based on the CDK4/6i received. The primary objective was to evaluate the incidence of pseudo-sCr elevation in the subgroups. sCr elevation was graded according to Common Terminology Criteria for Adverse Events Version 5. CDK4/6i-induced pseudo-sCr elevation was suspected when the sCr elevation could not be fully explained by other causes. Secondary endpoints included the grade, onset, duration, and clinical consequences of pseudo-sCr elevation. Incidence of pseudo-sCr elevation among the three groups were compared using the Chi-squared test. Descriptive statistics were used for pt characteristics and secondary endpoints. Results: In total, 143 pts were analyzed. Pseudo-sCr elevation was suspected in pts treated with palbo, ribo, and abema, 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 pts with CDK4/6i-induced pseudo-sCr elevation, all pts experienced either grade 1 (8.3%) or 2 (91.7%) events, with a median sCr increase from baseline to peak of 0.69 mg/dL (range, 0.39 – 2.9 mg/dL). The median onset from tx initiation to first sCr elevation was 33.5, 42, and 21.5 days, for palbo, ribo, and abema, respectively. Based on available data at study cutoff, 13 of the 24 pts with suspected pseudo-sCr elevation were still on tx with continued sCr elevation. Nine of 24 pts were no longer on CDK4/6i tx; none due to sCr elevation. Three of the 9 pts had sCr returned to baseline within 3 months of tx discontinuation. Conclusions: Pseudo-sCr elevation appears to be a class effect of CDK4/6i, with similar rates of sCr elevation observed across the three CDK4/6i currently FDA approved. Further analyses evaluating differences by age, race, and stage are ongoing.