Verzenios ® ▼ (abemaciclib)

This information is intended for UK registered healthcare professionals only as a scientific exchange in response to your search for information. Please refer to the link for full prescribing information: Verzenios Summary of Product Characteristics (SmPC)

How to manage haematologic toxicities under Verzenios® ▼ (abemaciclib)?

Dose modification is recommended for patients who develop Grade 3 or Grade 4 haematologic toxicities, including neutropenia, anemia, thrombocytopenia, and leukopenia.

Management Recommendations for Haematologic Toxicities

Please find dose modification recommendations in Table 1 and the grade definitions for haematologic toxicities according to the National Cancer Institute (NCI) Common Terminology Criteria of Adverse Events (CTCAE) inGrade Definitions According to the National Cancer Institute (NCI) Common Terminology Criteria of Adverse Events (CTCAE).

Monitor complete blood counts

  • prior to the start of abemaciclib therapy,

  • every two weeks for the first two months,

  • monthly for the next two months, and

  • as clinically indicated. 1

Before treatment initiation,

  • absolute neutrophil counts (ANC) ≥1500/mm3,

  • platelets ≥100,000/mm3, and

  • haemoglobin ≥8 g/dL are recommended.1

Table 1.   Management recommendations for haematologic toxicities1

Toxicityab

Management recommendations

Grade 1 or 2

No dose adjustment required.

Grade 3

Suspend dose until toxicity resolves to Grade 2 or less.

Dose reduction is not required.

Grade 3, recurrent; or Grade 4

Suspend dose until toxicity resolves to Grade 2 or less.

Resume at next lower dose.

Patient requires administration of blood cell growth factors

Suspend abemaciclib dose for at least 48 hours after the last dose of blood cell growth factors was administered and until toxicity resolves to Grade 2 or less.

Resume at next lower dose unless the dose was already reduced for the toxicity that led to the use of the growth factor.

LLN = lower limit of normal

a NCI Common Terminology Criteria for Adverse Events (CTCAE)

b ANC: Grade 1: ANC < LLN - 1500/mm3; Grade 2: ANC 1000 - <1500/mm3; Grade 3: ANC 500 - <1000/mm3; Grade 4: ANC <500/mm3

Hematopoietic Growth Factor Support in the MONARCH-2 and MONARCH-3 Studies

Hematopoietic growth factors reduce the duration and severity of neutropenia and the risk of febrile neutropenia.2 Their administration was permitted in the MONARCH-3 and MONARCH-2 study in accordance with the ASCO guidelines.2-5

  • 15 patients (4.6%) received hematopoietic growth factors in MONARCH-3, and6

  • 31 patients (7.0%) in the MONARCH-2 study.6

Filgrastim was the most commonly used hematopoietic growth factor in the MONARCH 2 and MONARCH 3 studies.4,5

If the administration of growth factors is required, then refer to Table 1 for dose modification and management.

Incidence of Hematologic Toxicities

Please find the incidence of haematologic toxicities with abemaciclib plus endocrine therapy in Table 2.

Table 2. Adverse reactions of the System Organ Class Blood and Lymphatic System Disorders reported in phase 3 studies of abemaciclib in combination with endocrine therapy (N=768)

System organ class

  Frequency

    Preferred Term

Abemaciclib plus endocrine therapya

All Grades Toxicity

(%)

Grade 3 Toxicity

(%)

Grade 4 Toxicity

(%)

Blood and lymphatic system disorders

  Very common 

   Neutropenia 

   Leukopenia

   Anaemia  

   Thrombocytopenia

 Common   

   Lymphopenia

 Uncommon

   Febrile neutropenia





  45.1

  25.7

 30.1

14.3



 7.3





0.9





 22.9

   8.5

   7.0

   2.2

 

  3.0





    0.7





 2.5

0.3

0.1

1.0 



0.1

 



0.1

a Abemaciclib in combination with letrozole, anastrozole, or fulvestrant.

Haematologic Toxicity of Special Interest - Neutropenia

Neutropenia

  • was reported frequently (45.1%) and a

  • Grade 3 or 4 decrease in neutrophil counts (based on laboratory findings) was reported in 28.2% of patients receiving abemaciclib in combination with aromatase inhibitors or fulvestrant.1 

  • Febrile neutropenia was reported in 0.9% patients.1

  • Fatal events occurred in <1% of patients.1

The median time

  • to onset of Grade 3 or 4 neutropenia was 29 to 33 days, and 

  • to resolution was 11 to 15 days.1

References

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

2. Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the use of WBC growth factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Onc. 2015;33(28):3199-3212. https://doi.org/10.1200/JCO.2015.62.3488

3. Dickler 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

4. Sledge 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

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

6. Rugo HS, Huober J, Llombart-Cussac A, et al. Management of abemaciclib associated adverse events in patients with HR+, HER2- advanced breast cancer: analysis of the MONARCH trials. Poster presented at: Annual Meeting of the European Society for Medical Oncology (ESMO) European Cancer Congress (ECC); October 19-23, 2018; Munich, Germany. https://www.esmo.org/content/download/149891/2691140/file/EMSO-2018-Abstract-Book-partial-version.pdf

7. US Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE). Version 4.03. May 28, 2009. Updated June 14, 2010. Accessed March 15, 2021. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf

Grade Definitions According to the National Cancer Institute (NCI) Common Terminology Criteria of Adverse Events (CTCAE)

In the abemaciclib clinical trials, toxicities were graded according to the NCI CTCAE Version 4.03.5

The grade definitions for hematologic toxicities are shown in Table 3.

Table 3. NCI CTCAE Grade Definitions7

Adverse Event

Grade 1

Grade 2

Grade 3

Grade 4

Neutrophil
count
decreased
a

<LLN-1500/mm3;
<LLN-1.5 x 109 /L

<1500-1000/mm3;
<1.5-1.0 x 109 /L

<1000-500/mm3;
<1.0-0.5 x 109 /L

<500/mm3;
<0.5 x 109 /L

White blood
cell count
decreased
b

<LLN-3000/mm3;
<LLN-3.0 x 109 /L

<3000-2000/mm3;
<3.0-2.0 x 109 /L

<2000-1000/mm3;
<2.0-1.0 x 109 /L

<1000/mm3;
<1.0 x 109 /L

Anemiac

<LLN-10.0 g/dL;
<LLN-6.2 mmol/L;
<LLN-100 g/L

<10.0-8.0 g/dL;
<6.2-4.9 mmol/L;
<100-80 g/L

<8.0 g/dL;
<4.9 mmol/L;
<80 g/L;
transfusion indicated

Life-threatening consequences;
urgent intervention indicated

Platelet
count
decreased
d

<LLN-75,000/mm3;
<LLN-75.0 x 109 /L

<75,000-50,000/mm3;
<75.0-50.0 x 109 /L

<50,000-25,000/mm3;
<50.0-25.0 x 109 /L

<25,000/mm3;
<25.0 x 109 /L

Abbreviations: CTCAE = Common Terminology Criteria for Adverse Events version 4.03; LLN = lower limit of normal; NCI = National Cancer Institute.

a Finding based on laboratory test results that indicate a decrease in number of neutrophils in a blood specimen.

b Finding based on laboratory test results that indicate a decrease in number of white blood cells in a blood specimen.

c Disorder characterized by a reduction in the amount of hemoglobin in 100 ml of blood.

d Finding based on laboratory test results that indicate a decrease in number of platelets in a blood specimen.

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: May 27, 2021


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