Background: Ribociclib is a cyclin-dependent kinase 4 and 6 inhibitor approved for treatment of advanced or metastatic hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative breast cancer at a dose of 600 mg and adjuvantly for high-risk, early-stage HR+, HER2- breast cancer at a dose of 400 mg . While ribociclib has resulted in improved cancer-related outcomes, the incidence of ribociclib-induced serum creatinine (SCr) elevations has been reported in 8-65% of patients in phase 3 trials although up to 73% of those cases are attributed to a phenomenon known as pseudo-acute kidney injury (AKI). The proposed mechanism is thought to be due to ribociclib’s competitive inhibition of renal tubular secretion transporters, OCT2, MATE1, MATE2-K, blocking creatinine secretion into urine without affecting actual glomerular filtration rate. Cystatin C is an alternative surrogate marker of renal function that is not affected by ribociclib’s inhibition of renal tubular transporters and thus may be utilized to distinguish pseudo-AKI from true kidney injury. This study aimed to further describe the nature and clinical significance of ribociclib-induced SCr elevation in patients with HR+, HER2- breast cancer in a real-world setting.
Methods: This IRB approved, single-center, retrospective chart review included all adult patients prescribed ribociclib for HR+, HER2- breast cancer at Emory Winship Cancer Institute between October 2022 and August 2025. Patients were excluded if ribociclib was prescribed by an external provider, used for investigational purposes, or if baseline SCr documentation at least 6 months prior to ribociclib initiation was missing. The primary outcome was incidence of ribociclib-induced SCr elevation, defined as ≥ grade 1 per CTCAE v5.0. Cystatin C, defined as > 0.95 mg/dL, was utilized to assess reduced renal function. Use of concomitant nephrotoxic medications including CT contrast, zoledronic acid, diuretics, NSAIDs, metformin, antihypertensives, and antibiotics was assessed.
Results: 168 females and 2 males were reviewed, median age 58 years old. The majority (139 patients, 81.7%), were prescribed ribociclib for metastatic disease; 31 (18.2%) adjuvantly. Ribociclib-induced SCr elevation occurred in 49 patients (28.8%). Of those patients, 40 (81.6%) had metastatic disease, the initial dose was 600 mg for 36 (73.5%), and 47 (95.9%) were prescribed concomitant nephrotoxic medications though not statistically significant (p-value, 0.515). Median absolute change in SCr from baseline was 0.45 mg/dL (range, 0.34-0.54 mg/dL); median time to SCr elevation was 33 days (range, 15-83 days). Most events were grade 2 (35, 71.4%); 14 (28.6%) were grade 1. Of those with elevated SCr, 5 patients (10.2%) had true kidney injury as indicated by an elevated cystatin C warranting consideration of dose interruption or reduction. Median time to SCr recovery was 155 days (range, 27-316 days).
Conclusion: Ribociclib-induced SCr elevation often occurred within the first or second cycle and remained elevated yet stable through the first six cycles. The majority were grade 1 or 2 events and did not require dose reductions or interruptions.
