Dose adjustment is not necessary in patients with mild or moderate renal impairment (creatinine clearance [CrCL] ≥30-89 mL/min, estimated by Cockcroft-Gault [CG]).1,2

In a population pharmacokinetic analysis, mild and moderate renal impairment had no effect on the exposure of abemaciclib.1

The population pharmacokinetic analysis evaluated 989 individuals including

• 383 individuals with mild renal impairment (60 mL/min ≤ CrCL <90 mL/min), and
• 127 individuals with moderate renal impairment (30 mL/min ≤ CrCL <60 mL/min).1

There are no data in patients

• with severe renal impairment (CrCL <30 mL/min, CG)
• with end stage renal disease, or
• on dialysis.1,2
  

Two case studies are available that discuss the use of abemaciclib in patients on dialysis Case studies of two patients with end-stage renal disease and on dialysis 

Studies indicated that hepatic metabolism is the main route of clearance for abemaciclib. Abemaciclib is metabolized to several metabolites primarily by cytochrome P450 (CYP) 3A.1

Abemaciclib should be administered with caution in patients with severe renal impairment, with close monitoring for signs of toxicity. Below you will find information about the metabolism and elimination of abemaciclib. 
Please review the Verzenios Summary of Product Characteristics, particularly the section: 

• 5.2 Pharmacokinetic properties

Other measures of renal function (such as blood urea nitrogen, cystatin C, or calculated glomerular filtration rate based on cystatin C) should be used as an alternative to either serum creatinine or creatinine-based calculated estimates of glomerular filtration rate (GFR) if

• serum creatinine rise is progressive after the first cycle
• there are other indications of renal injury (eg, proteinuria, etc.), or
• a patient has a need for precise GFR assessment (such as concomitant medications that effect kidney function).7,11,12

Creatinine may not be an accurate method to assess renal function in these patients.7,11-13

Serum or plasma cystatin C measurement is an automated test that is readily available and does not require special processing or handling of the blood sample.14

Cystatin C is a small protein that is produced by all nucleated cells and found in body fluids, including serum. It is formed at a constant rate and due to its small size is freely filtered by the glomeruli. Cystatin C is not secreted and is fully reabsorbed and broken down by the renal tubules.15 Cystatin C has been consistently found to have a higher correlation with standard measures of GFR when compared with creatinine.16

A retrospective analysis of adverse drug reactions (ADRs) related to abemaciclib (data retrieved from Q3 of 2017 to Q2 of 2024) using the Food and Drug Administration Adverse Event Reporting System (FAERS) was conducted which focused on ADRs associated with kidney injuries.17

This analysis identified 10,757 reports related to abemaciclib. Among these, 8 kidney-related adverse reactions were identified, such as increased blood creatinine, renal disorders, decreased glomerular filtration rate, increased blood urea, and abnormal renal function tests.17

Kidney injuries associated adverse reactions of abemaciclib ranked by frequency in the FAERS database is presented in Kidney Injuries Associated with Clinical Adverse Reactions of Abemaciclib Ranked by Frequency (N) at the Preferred Term Level in FAERS Database Calculated by Disproportionality Analysis.17

The case studies discuss the treatment of two patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) and end-stage renal disease (ESRD) who were undergoing haemodialysis. Both patients received standard hormonal therapy plus abemaciclib 100 mg twice daily under strict monitoring for toxicity.18 

Patient 1. The first patient was a 68-year-old woman who had been on adjuvant letrozole for 3 years before experiencing disease progression. She received fulvestrant and abemaciclib, and despite experiencing grade 2 diarrhoea initially (after 10 days), the side effect was managed with dietary changes and loperamide. The patient showed a partial response to the treatment after 12 months, and was at the time of publication of the case report still under the same treatment with no sign of progressive disease.18

Patient 2. A 47-year-old woman who had previously undergone surgery and received adjuvant LHRH and tamoxifen for 5 years. She developed metastatic disease and was treated with letrozole and abemaciclib. The patient tolerated the treatment well, with only mild grade 1 neutropenia and anaemia, recorded after 4 months of treatment without need of dose modification. No further safety signals, e.g. thrombocytopenia, deep venous thrombosis or interstitial lung disease were observed. At time of publication and after 9 months of treatment, the patient presented with stable disease.18

Throughout the treatment, both patients were closely monitored for toxicity, renal function, and other potential adverse effects. Renal function, as measured by creatinine and blood urea nitrogen (BUN) levels, remained relatively stable during the treatment period.18

Measurements of creatinine clearance of both patients throughout the treatment with abemaciclib are shown in Creatinine clearance throughout the treatment period with abemaciclib

The case studies highlight the importance of joint decision-making, expectation setting and appropriate counselling when treating patients with metastatic breast cancer and end-stage renal disease. Limited data are available in the medical literature regarding the use of cyclin-dependent kinase inhibitors (CDKIs) in this patient population. In these two cases, abemaciclib in combination with antihormonal therapy showed good response and safety. Mild diarrhoea and asthenia were the most common adverse events observed.18

Links to references and third-party websites are provided solely for your convenience and to facilitate easy access to the sources cited.