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Verzenios ® (abemaciclib)
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Are dose adjustments of Verzenios® (abemaciclib) required for patients with renal impairment?
Dose adjustments are not required for patients with mild or moderate renal impairment. Although no data is available on patients with severe impairment or on dialysis, two case studies are discussed below.
Content overview
Relevant information from the summary of product characteristics
No dose adjustments are necessary in patients with mild or moderate renal impairment. There are no data regarding abemaciclib administration in patients with severe renal impairment, end stage renal disease, or in patients on dialysis. The product has been shown to increase serum creatinine due to inhibition of renal tubular secretion transporters, without affecting glomerular function.1
For complete information, please refer to the Verzenios Summary of Product Characteristics, in particular the sections
- 4.2 Posology and method of administration
- 4.8 Undesirable effects
- 5.2 Pharmacokinetic properties
Effect of mild and moderate renal impairment on the exposure of abemaciclib
In a population pharmacokinetic analysis, mild and moderate renal impairment had no effect on the exposure of abemaciclib.2
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).2
Effect on serum creatinine
Effect on serum creatinine in advanced or metastatic breast cancer trials
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.2
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 reductions, omissions and discontinuations in MONARCH 2 and MONARCH 3 due to increased creatinine shows the detailed breakdown from the studies.6
|
MONARCH 2 |
MONARCH 3 |
Dose reduction due to increased creatinine |
0.5% |
2.4% |
Dose omission due to increased creatinine |
1.4% |
1.6% |
Discontinued treatment due to increased creatinine |
0% |
1.2% |
Effect on serum creatinine in early breast cancer
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.7
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, 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.2
Another prespecified overall survival interim analysis was recently conducted on the monarchE study data. At data cutoff on July 3, 2023, the median follow-up time was 54 months. There were no new safety concerns identified in the long-term follow-up with no cumulative or persistent symptoms observed following completion of treatment.8
In monarchE, 10 (0.4%) patients discontinued abemaciclib treatment due to increased blood creatinine.9
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 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.13
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.14 Cystatin C has been consistently found to have a higher correlation with standard measures of GFR when compared with creatinine.15
Abemaciclib-associated Kidney Injuries: A Retrospective Analysis of the United States Food and Drug Administration Adverse Events Reporting System
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.16
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.16
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.16
Preferred Term |
N |
Increased blood creatinine |
210 |
Renal disorder |
47 |
Decreased glomerular filtration rate |
27 |
Increased blood urea |
20 |
Hydronephrosis |
11 |
Abnormal renal function test |
10 |
Increased creatinine renal clearance |
6 |
Increased cystatin C |
3 |
Abbreviation: FAERS = Food and Drug Administration Adverse Event Reporting System.
Case studies of two patients with end-stage renal disease and on dialysis
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.17
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.17
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.17
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.17
Measurements of creatinine clearance of both patients throughout the treatment with abemaciclib are shown in Creatinine clearance throughout the treatment period with abemaciclib
Data taken from Table 1: Renal function during treatment with abemaciclib17
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.17
References
1Verzenios [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.
2Data on file, Eli Lilly and Company and/or one of its subsidiaries.
3Dickler MN, Tolaney SM, Rugo HS, et al. MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR+/HER2− metastatic breast cancer. Clin Cancer Res. 2017;23(17):5218-5224. http://dx.doi.org/10.1158/1078-0432.CCR-17-0754
4Sledge GW Jr, Toi M, Neven P, et al. MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2− advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 2017;35(25):2875-2884. https://doi.org/10.1200/JCO.2017.73.7585
5Goetz MP, Toi M, Campone M, et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017;35(32):3638-3646. https://doi.org/10.1200/jco.2017.75.6155
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
7Johnston 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
8Rastogi P, O'Shaughnessy J, Martin M, et al. Adjuvant abemaciclib plus endocrine therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative, high-risk early breast cancer: results from a preplanned monarchE overall survival interim analysis, including 5-year efficacy outcomes. J Clin Oncol. 2024;42(9):987-993. https://doi.org/10.1200/jco.23.01994
9Rugo 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
10Milburn 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
11Shlipak 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
12Chappell 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
13Shlipak 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
14Chew 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/
15Inker 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
16Xu X, Guo X, Chen J, et al. Abemaciclib-associated kidney injuries: A retrospective analysis of the United States Food and Drug Administration adverse events reporting system. J Int Med Res. 2025;53(3):3000605251325961. https://doi.org/10.1177/03000605251325961
17Gebbia V. Abemaciclib in Patients with End-Stage Renal Disease and Advanced Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: A Report of 2 Cases. Case Rep Oncol. 2022;15(1):305-311. Published 2022 Mar 28. doi:10.1159/000523856 .
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Date of Last Review: 04 April 2025