Verzenios ® ▼ (abemaciclib)

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What is Verzenios® ▼ (abemaciclib) effect on serum creatinine in early breast cancer?

Abemaciclib causes a reversible increase in serum creatinine without decreasing renal function.

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Effect on Serum Creatinine in monarchE

In monarchE, increased serum creatinine was the most common laboratory abnormality reported in abemaciclib-treated patients with 

  • 47.9% reporting a grade 1 event
  • 51.0% reporting a grade 2 event, and
  • 0.4% reporting a grade 3 event.1

In monarchE, 10 (0.4%) patients discontinued abemaciclib treatment due to increased blood creatinine.2

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).3-5

Creatinine may not be an accurate method to assess renal function in these patients.3-6

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.7 Cystatin C has been consistently found to have a higher correlation with standard measures of GFR when compared with creatinine.8

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.9

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.10 The trial is active but not recruiting.11

Effect on Serum Creatinine in monarchE

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.10 

In the monarchE trial, increased serum creatinine was the most common laboratory abnormality reported in the abemaciclib + ET arm with 

  • 47.9% reporting a Grade 1 event
  • 51.0% reporting a Grade 2 event, and
  • 0.4% reporting a Grade 3 event.1

In monarchE, 10 patients (0.4%) discontinued abemaciclib treatment due to increased creatinine.12

Alternative Testing for Renal Impairment

Other measures of renal function (such as 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).3,4

Creatinine may not be an accurate method to assess renal function in these patients.3,4,6

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.7 Cystatin C has been consistently found to have a higher correlation with standard measures of GFR when compared with creatinine.8

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.9

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.10 The trial is active but not recruiting.11

References

1Data on file, Eli Lilly and Company and/or one of its subsidiaries.

2Rugo 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

3Milburn 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

4Shlipak 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

5Rugo 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

6Chappell 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

7Chew 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/

8Inker 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

9Shlipak 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

10Johnston 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

11Endocrine 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

12Rugo HS, O'Shaughnessy J, Song C, et al. Safety outcomes from monarchE: phase 3 study of abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2−, node-positive, high risk, early breast cancer. Poster presented at: 17th Annual St. Gallen International Breast Cancer Conference (SGBCC Virtual); March 17-21, 2021. 

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Date of Last Review: 25 August 2022


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