Abemaciclib has been shown to increase serum creatinine due to inhibition of renal tubular transporters without affecting glomerular function. In clinical studies, increases in serum creatinine occurred within the first month of abemaciclib dosing, remained elevated but stable through the treatment period, and were reversible upon treatment discontinuation.

Alternative markers such as blood urea nitrogen, cystatin C, or calculated glomerular filtration rate, which are not based on creatinine, may be considered to determine whether renal function is impaired (see Alternative testing for renal impairment for more information).1

Abemaciclib has been shown to increase serum creatinine due to inhibition of renal tubular secretion transporters, without affecting glomerular function.1,2

In the MONARCH 1, MONARCH 2, and MONARCH 3 trials, increased serum creatinine was the most common laboratory abnormality reported with 98%, 97%, and 96% of patients, respectively, having a grade 1 or 2 event.3-5

In healthy subjects, mean maximum creatinine increases of approximately 20% to 35% over baseline values occurred at about 24 hours post-dose and then returned to baseline at about 336 hours (14 days) post-dose.1

In clinical studies, increases in serum creatinine (mean increase 0.2-0.3 mg/dL)

• occurred within the first 28-day cycle of abemaciclib dosing
• remained elevated but stable throughout the treatment period, and
• were reversible upon treatment discontinuation.1,6,7

The incidence of dose reduction, omission, and discontinuation due to elevated creatinine was <2.5% across both MONARCH 2 and MONARCH 3 studies and only occurred in the abemaciclib arms. Dose reduction due to increased creatinine was reported in 0.5% and 2.4% of patients in the MONARCH 2 and MONARCH 3 studies.6 

Dose omission due to elevated creatinine occurred in 1.4% and 1.6% of the patients in MONARCH 2 and MONARCH 3 studies. No patients in the MONARCH 2 study discontinued treatment due to increased creatinine, while 1.2% of patients in the MONARCH 3 study discontinued treatment for that reason.6

A prespecified overall survival interim analysis (OS IA2) was recently conducted on the monarchE study data. At the data cutoff date (July 1, 2022), the median follow-up time for the overall population was 42 months and all treated patients were off abemaciclib treatment. The incidence of increased blood creatinine (regardless of attribution) in monarchE at this analysis is presented in Incidence of Increased Blood Creatinine at OS IA2 Analysis of monarchE.8

While Incidence of Increased Blood Creatinine at OS IA2 Analysis of monarchE shows the incidence of increased blood creatinine (regardless of attribution) in monarchE as a TEAE, increased serum creatinine was the most common laboratory abnormality reported during abemaciclib treatment with 99% of abemaciclib-treated patients having a grade 1 or 2 event.1

In monarchE, 10 (0.4%) patients discontinued abemaciclib treatment due to increased blood creatinine.9

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).6,10,11

Creatinine may not be an accurate method to assess renal function in these patients.6,10-12

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.13 Cystatin C has been consistently found to have a higher correlation with standard measures of GFR when compared with creatinine.14

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.15

The management of adverse reactions may require dose interruptions or dose reductions or both. Below you will find information about the recommendations on dose adjustments. Please review the Verzenios Summary of Product Characteristics, particularly the section:

• 4.2 Posology and method of administration
• 
  

CTCAE Grade definitions for elevated serum creatinine are shown in CTCAE Grades for elevated serum creatinine

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