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Verzenios ® ▼ (abemaciclib)
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Are dose adjustments of Verzenios® (abemaciclib) required for patients with renal impairment?
No dose adjustments are necessary in patients with mild or moderate renal impairment. Abemaciclib should be administered with caution in patients with severe renal impairment, with close monitoring for signs of toxicity.
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
In a population pharmacokinetic analysis, mild and moderate renal impairment did not affect 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
No data in patients with severe renal impairment, end-stage renal disease or on dialysis
While abemaciclib is not contraindicated, we have no data in patients
Administer abemaciclib with caution in patients with severe renal impairment and closely monitor for signs of toxicity.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
Metabolism and elimination
Studies indicated that hepatic metabolism is the main route of clearance for abemaciclib. Abemaciclib is metabolized to several metabolites primarily by cytochrome P450 3A.1
The geometric mean hepatic clearance of abemaciclib was 21.8 L/h (39.8% coefficient of variation [CV]), and the mean plasma elimination half-life for abemaciclib in patients was 24.8 hours (52.1% CV). After a single oral dose of radiolabeled abemaciclib, approximately 81% of the dose was recovered in feces and approximately 3.4% recovered in urine. The majority of the dose eliminated in feces was metabolites.1
Effect on serum creatinine
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.4-6
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)
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. shows the detailed breakdown from the studies.7
Dose reduction due to increased creatinine
Dose omission due to increased creatinine
Discontinued treatment due to increased creatinine
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
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.12 Cystatin C has been consistently found to have a higher correlation with standard measures of GFR when compared with creatinine.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
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.15
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.15
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.15
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.15
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.15
1Data on file, Eli Lilly and Company and/or one of its subsidiaries.
2Verzenios [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.
3Tolaney S, Lam AQ, Mukundan S, et al. Analysis of renal function in MONARCH 1: A phase 2 study of abemaciclib, a CDK4 & 6 inhibitor, as monotherapy, in patients with HR+/HER2- breast cancer, after chemotherapy for metastatic breast cancer (MBC). Cancer Res. 2017;77(4 suppl):P6-15-01. American Association for Cancer Research abstract P6-15-01. http://cancerres.aacrjournals.org/content/77/4_Supplement/P6-15-01
4Dickler 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
5Sledge 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
6Goetz 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
7Rugo 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
8Verzenio [package insert]. Indianapolis, IN: Eli Lilly and Company; 2021.
9Milburn 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
10Shlipak 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
11Chappell 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
12Chew 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/
13Inker 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
14Shlipak 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
15Gebbia 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 .
Date of Last Review: 28 October 2021