Verzenios ® ▼ (abemaciclib)

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What are the most frequent adverse events associated with Verzenios® ▼ (abemaciclib) in early breast cancer?

The most common adverse reactions in monarchE were diarrhea, fatigue, neutropenia, and nausea.

UK_cFAQ_ABE028_MOST_FREQUENT_ADVERSE_EVENTS_EBC
UK_cFAQ_ABE028_MOST_FREQUENT_ADVERSE_EVENTS_EBC
en-GB

Abemaciclib: most frequent adverse events in early breast cancer (EBC)

Abemaciclib in Combination With Endocrine Therapy (monarchE)

Information on the AEs that are considered clinically relevant to abemaciclib are summarized in Clinically Relevant AEs Observed in At Least 10% of Patients in Abemaciclib + ET arm in monarchE. Data on the ET only arm are included for comparison1.

Clinically Relevant AEs Observed in At Least 10% of Patients in Abemaciclib + ET arm in monarchE1

 

Abemaciclib + ET

N=2791

ET Alone

N=2800

Event Term, %

Any Grade

Grade 1

Grade 2

Grade >3

Any Grade

Grade 1

Grade 2

Grade >3

Patients with ≥1 AEa

97.9

6.8

43.7

47.4

87.2

24.8

48.3

14.2

Diarrhea

82.6

44.8

30.1

7.7b

7.8

6.0

1.6

0.2

Infectionsc

47.7

8.4

34.5

4.7

36.4

8.0

25.9

2.6d

Neutropenia

45.2

6.3

19.8

19.1

5.2

2.2

2.3

0.7

Fatigue

39.2

22.3

14.1

2.8

16.6

12.8

3.7

0.1

Nausea

28.5

21.4

6.6

0.5

8.3

6.5

1.8

0.1

Anemia

23.5

13.6

8.1

1.8

3.4

2.5

0.5

0.4

Vomiting

16.7

12.8

3.5

0.5

4.4

3.3

1.0

0.1

Headache

17.9

13.7

4.0

0.2

13.8

10.6

3.0

0.1

Stomatitise

13.1

10.6

2.3

0.1

5.0

4.5

0.5

0

Thrombocytopenia

12.6

9.5

2.0

1.2

1.6

1.3

0.2

0.1

Decreased appetite

11.5

8.6

2.3

0.6

2.2

1.8

0.3

0.1

ALT increase

10.4

5.7

2.3

2.4

4.9

3.5

0.8

0.6

Rash

10.3

8.1

1.8

0.4

4.0

3.3

0.7

0

AST increase

10.1

6.8

1.5

1.8

4.3

3.3

0.5

0.5

Abbreviations: AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; CTCAE = Common Terminology Criteria for Adverse Events; ET = endocrine therapy; NCI = National Cancer Institute.

aThe severity of AEs were recorded by investigators and graded by the NCI-CTCAE v4.

b1 grade 5 event.

cInfection is a composite term that includes all reported preferred terms that are part of the infections and infestations system organ class.

d4 grade 5 events.

eStomatitis is a consolidated term that includes mouth ulceration, mucosal inflammation, oropharyngeal pain, stomatitis.

The most common TEAEs in the abemaciclib treatment arm are diarrhea, neutropenia, and fatigue as seen in Most Common TEAEs in the Abemaciclib Arm (N=2791) or ET Alone Arm (N=2800) in the Primary Outcome Analysis of monarchE. The most common TEAEs in the ET alone arm are arthralgia, hot flush, and fatigue. Other TEAEs are listed in Most Common TEAEs in the Abemaciclib Arm (N=2791) or ET Alone Arm (N=2800) in the Primary Outcome Analysis of monarchE.2

Most Common TEAEs in the Abemaciclib Arm (N=2791) or ET Alone Arm (N=2800) in the Primary Outcome Analysis of monarchE2

TEAE, %

Abemaciclib + ET
Any Grade

Abemaciclib + ET
Grade 3

Abemaciclib + ET
Grade 4

ET Alone
Any Grade

ET Alone
Grade 3

ET Alone
Grade 4

Diarrhea

82.6

7.7

0

7.8

0.2

0

Neutropenia

45.2

18.5

0.6

5.2

0.6

0.1

Fatigue

39.2

2.8

0

16.6

0.1

0

Leukopenia

37.2

10.8

0.1

6.3

0.4

0

Abdominal pain

34.4

1.3

0

9.0

0.3

0

Nausea

28.5

0.5

0

8.3

<0.1

0

Anemia

23.5

1.8

<0.1

3.4

0.3

<0.1

Arthralgia

22.0

0.3

0

33.1

0.7

0

Hot flush

14.5

0.1

0

21.8

0.4

0

VTEa
PEa

2.4
0.9

1.1
0.8

0.2
0.1

0.6
0.1

0.2
0.1

0b
0b

ILDac

2.9

0.4

0d

1.2

<0.1

0

Abbreviations: AE = adverse event; ET = endocrine therapy; ILD = interstitial lung disease: MedDRA = Medical Dictionary for Regulatory Activities; PE = pulmonary embolism; TEAE = treatment-emergent adverse event; VTE = venous thromboembolic event.

aOther AEs of Interest.

bOne grade 5 event occurred.

cTerm is based on the standard MedDRA query.

dOne grade 5 event occurred.

The overall incidence of SAEs was higher in the abemaciclib + ET arm (13.3%) compared to the ET alone (7.8%). 1

Deaths due to AEs on study or ≤30 days of discontinuation were as follows:

  • 11 patients (0.4%) in the abemaciclib + ET arm:
    • cardiac arrest (1)
    • cardiac failure (2)
    • cerebral hemorrhage (1)
    • cerebrovascular accident (1)
    • diarrhea (1)
    • general physical deterioration (1)
    • hypoxia (1)
    • myocardial infarction (1)
    • pneumonitis (1)
    • ventricular fibrillation (1).
  • 9 patients (0.3%) in the ET-only arm:
    • death (1)
    • gastrointestinal adenocarcinoma (1)
    • influenza (1)
    • pleural effusion (1)
    • pneumonia (1)
    • pulmonary embolism (1)
    • septic shock (1)
    • sudden death (1)
    • urosepsis (1).1

Adverse Events of interest in monarchE

Diarrhea

Diarrhea typically occurred early, and was managed with abemaciclib dose adjustment and antidiarrheal medication. Patients were instructed to initiate antidiarrheal agents at the first sign of loose stools and drink fluids. If grade ≤1 was not reached within 24 hours, treatment was temporarily discontinued until diarrhea resolved. Dose reductions, omissions, and modifications occurred for grade ≥3 or persistent grade 2 diarrhea.1,3,4

Increases in Serum Creatinine

Abemaciclib has been shown to increase serum creatinine due to inhibition of renal tubular secretion transporters, without affecting glomerular function.3,4

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 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).5,6

Creatinine may not be an accurate method to assess renal function in these patients.5-7

Conclusions

The overall safety profile of abemaciclib in monarchE is generally consistent with the established safety profile of abemaciclib, with no new safety concerns.1

References

1Rugo 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.

2O'Shaughnessy JA, Johnston S, Harbeck N, et al. Primary outcome analysis of invasive disease-free survival for monarchE: abemaciclib combined with adjuvant endocrine therapy for high risk early breast cancer. Abstract presented at: 43rd Annual San Antonio Breast Cancer Symposium (SABCS Virtual); December 8-11, 2020. Accessed December 9, 2020. https://www.abstractsonline.com/pp8/#!/9223/presentation/664

3Data on file, Eli Lilly and Company and/or one of its subsidiaries.

4Verzenios [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

5Milburn 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

6Shlipak 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

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

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: 28 June 2021


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