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Verzenios ® ▼ (abemaciclib)
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What effect does Verzenios® (abemaciclib) have on serum creatinine in EBC patients?
Abemaciclib causes a reversible increase in serum creatinine without decreasing renal function.
Increased Serum Creatinine With Abemaciclib
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
Effect on Serum Creatinine in monarchE
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.2
TEAEa, n (%) |
Abemaciclib + ET |
ET Alone |
||||||
Grade 1-2 |
Grade 3 |
Grade 4 |
Grade 5 |
Grade 1-2 |
Grade 3 |
Grade 4 |
Grade 5 |
|
Blood creatinine increased |
308 (11.0) |
3 (0.1) |
0 |
0 |
28 (1.0) |
0 |
0 |
0 |
Abbreviations: ET = endocrine therapy; OS IA2 = overall survival interim analysis; TEAE = treatment-emergent adverse event.
Data cutoff: July 1, 2022.
aAdverse event was assessed in the safety population which included all treated patients.
In monarchE, 10 (0.4%) patients discontinued abemaciclib treatment due to increased blood creatinine.3
Alternative Testing for Renal Impairment
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).4-6
Creatinine may not be an accurate method to assess renal function in these patients.4-7
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.8 Cystatin C has been consistently found to have a higher correlation with standard measures of GFR when compared with creatinine.9
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.10
The monarchE Study
monarchE is an open-label, randomized, phase 3 trial comparing adjuvant abemaciclib 150 mg twice daily plus endocrine therapy (ET) versus ET alone for a two-year duration, in 5,637 patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive, early breast cancer (EBC) at high risk of recurrence.
At the end of the study treatment, patients entered physician-directed ET follow up for a total of 5-10 years, as clinically indicated.11 The trial is active but not recruiting.12
References
1Data on file, Eli Lilly and Company and/or one of its subsidiaries.
2Johnston SRD, Toi M, O'Shaughnessy J, et al; monarchE Committee Members. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023;24(1):77-90. https://doi.org/10.1016/S1470-2045(22)00694-5
3Rugo HS, O’Shaughnessy J, Boyle F, et al; monarchE Committee Members. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: safety and patient-reported outcomes from the monarchE study. Ann Oncol. 2022;33(6):616-627. https://doi.org/10.1016/j.annonc.2022.03.006
4Milburn J, Jones R, Levy JB. Renal effects of novel antiretroviral drugs. Nephrol Dial Transplant. 2017;32(3):434-439. https://doi.org/10.1093/ndt/gfw064
5Shlipak MG, Matsushita K, Ärnlöv J, et al. Cystatin C versus creatinine in determining risk based on kidney function. N Engl J Med. 2013;369(10):932-943. https://doi.org/10.1056/NEJMoa1214234
6Rugo HS, Huober J, Garcia-Saenz JA, et al. Management of abemaciclib-associated adverse events in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: safety analysis of MONARCH 2 and MONARCH 3. Oncologist. 2021;26(1):e53-e65. http://dx.doi.org/10.1002/onco.13531
7Chappell JC, Turner PK, Pak YA, et al. Abemaciclib inhibits renal tubular secretion without changing glomerular filtration rate. Clin Pharmacol Ther. 2019;105(5):1187-1195. https://doi.org/10.1002/cpt.1296
8Chew JSC, Saleem M, Florkowski CM, George PM. Cystatin C – a paradigm of evidence based laboratory medicine. Clin Biochem Rev. 2008;29(2):47-62. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2533150/
9Inker LA, Schmid CH, Tighiouart H, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med. 2012;367(1):20-29. https://doi.org/10.1056/NEJMoa1114248
10Shlipak MG, Mattes MD, Peralta CA. Update on cystatin C: incorporation into clinical practice. Am J Kidney Dis. 2013;62(3):595-603. https://doi.org/10.1053/j.ajkd.2013.03.027
11Johnston SRD, Harbeck N, Hegg R, et al; monarchE Committee Members and Investigators. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2−, node-positive, high-risk, early breast cancer (monarchE). J Clin Oncol. 2020;38(34):3987-3998. https://doi.org/10.1200/JCO.20.02514
12Endocrine therapy with or without abemaciclib (LY2835219) following surgery in participants with breast cancer (monarchE). ClinicalTrials.gov identifier: NCT03155997. Updated January 24, 2022. Accessed October 1, 2021. https://clinicaltrials.gov/show/NCT03155997
Date of Last Review: 08 February 2023