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Verzenios ® ▼ (abemaciclib)

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How to manage haematologic toxicities under Verzenios® ▼ (abemaciclib) in early breast cancer?

Neutropenia, leukopenia, anemia, lymphopenia, and thrombocytopenia were the most commonly reported hematologic adverse reactions in monarchE.

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Incidence of Hematologic Toxicities in monarchE

After 27.1 median months follow-up (additional follow-up 1 [AFU1] analysis), neutropenia, leukopenia, anemia, lymphopenia, and thrombocytopenia were the most common hematologic adverse events as shown in Hematologic Adverse Events at the AFU1 Analysis in monarchE.1

Hematologic Adverse Events at the AFU1 Analysis in monarchE1





Adverse Event, N (%)

CTCAE Grade

Abemaciclib + ET
N=2791

ET Alone
N=2800

Any Grade

Grade 3

Grade 4

Any Grade

Grade 3

Grade 4

Neutropenia

1278 (45.8)

527 (18.9)

19 (0.7)

157 (5.6)

19 (0.7)

4 (0.1)

Leukopenia

1049 (37.6)

313 (11.2)

4 (0.1)

186 (6.6)

11 (0.4)

NAa

Anemia

681 (24.4)

56 (2.0)

1 (0.0)

104 (3.7)

9 (0.3)

1 (0.0)

Lymphopenia

395 (14.2)

148 (5.3)

3 (0.1)

96 (3.4)

13 (0.5)

0

Thrombocytopenia

373 (13.4)

28 (1.0)

8 (0.3)

52 (1.9)

2 (0.1)

2 (0.1)

Abbreviations: AFU1 = additional follow-up 1; CTCAE = Common Terminology Criteria for Adverse Events; ET = endocrine therapy; NA = not applicable.

aMax Grade 3 event (according to CTCAE v. 4)

At the primary outcome (PO) analysis, grade ≥3 neutropenic events were not associated with severe complications such as febrile neutropenia or severe infections. Additionally, neutropenia was the most frequently reported grade ≥3 AE, with a median time to onset of 30 days, a median duration of 16 days, and was rare after the first 6 months.2

After 15.5 median months of follow-up, at the preplanned interim analysis, any grade febrile neutropenia had occurred in 0.3% of abemaciclib treated patients.3 

Dose Modification for Hematologic Toxicities in monarchE

Dose modifications for neutropenia in monarchE are summarized in Dose Modifications Due to Neutropenia in the Abemaciclib Arm at the PO Analysis of monarchE.

Dose Modifications Due to Neutropenia in the Abemaciclib Arm at the PO Analysis of monarchE2

Dose Modification, %

Abemaciclib + ET
N=2791

Dose reductions

7.8

Dose holds

15.3

Discontinuations

0.9

Abbreviations: ET = endocrine therapy; PO = primary outcome.

Management Recommendations for Haematologic Toxicities

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

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. 4

Before treatment initiation,

  • absolute neutrophil counts (ANC) ≥1500/mm3,
  • platelets ≥100,000/mm3, and
  • haemoglobin ≥8 g/dL are recommended.4
  Management recommendations for haematologic toxicities4

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

aNCI Common Terminology Criteria for Adverse Events (CTCAE)

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

Growth Factor Support

Hematopoietic growth factors have been shown to reduce the risk of febrile neutropenia, as well as minimize the duration and severity of neutropenia as an adverse event.5,6 In monarchE, growth factors were permitted to be administered in accordance with American Society of Clinical Oncology (ASCO) guidelines.3

References

1Harbeck N, Rastogi P, Martin M, et al; monarchE Committee Members. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32(12):1571-1581. https://doi.org/10.1016/j.annonc.2021.09.015

2Rugo 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.

3Johnston 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

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

5Crawford J, Ozer H, Stoller R, et al. Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N Engl J Med. 1991;325(3):164-170. https://doi.org/10.1056/NEJM199107183250305

6Smith 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 Oncol. 2015;33(28):3199-3212. https://doi.org/10.1200/JCO.2015.62.3488

7Data on file, Eli Lilly and Company and/or one of its subsidiaries.

8US 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

Appendix

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 4.03.7

The grade definitions for hematologic toxicities are shown in NCI CTCAE Grade Definitions.

NCI CTCAE Grade Definitions8

Adverse Event

Grade 1

Grade 2

Grade 3

Grade 4

Neutrophil
count
decreaseda

<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
decreasedb

<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
decreasedd

<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.

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

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

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

dFinding 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: 17 February 2022

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