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  4. How to manage haematologic toxicities under Verzenios® (abemaciclib) in metastatic breast cancer
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Verzenios ® (abemaciclib)

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How to manage haematologic toxicities under Verzenios® (abemaciclib) in metastatic breast cancer

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

UK_cFAQ_ABE026_HEMATOLOGIC_DISORDERS_MBC
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Content Overview

Management Recommendations for Haematologic Toxicities

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

Incidence of Haematologic Toxicities

  • Haematologic Toxicity of Special Interest - Neutropenia

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

References

Management Recommendations for Haematologic Toxicities

Please find

  • dose modification and management recommendations in Dose modification and management for haematologic toxicities
  • grade definitions for haematologic toxicities in NCI CTCAE Grade Definitions
    Dose modification and management for haematologic toxicities1

    The infographic illustrates the schedule of blood count monitoring and dose modification and management of haematologic toxicity with abemaciclib. 

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

    Haematopoietic growth factors reduce the risk of febrile neutropenia and the duration and severity of neutropenia.2,3

    In the MONARCH 3 and MONARCH 2 studies, doctors were allowed to give growth factors according to the American Society of Clinical Oncology (ASCO) guidelines.3-5

    • 15 patients (4.6%) received haematopoietic growth factors in MONARCH-3, and6
    • 31 patients (7.0%) in the MONARCH-2 study.6

    Filgrastim was the most commonly used haematopoietic growth factor in the MONARCH 2 and MONARCH 3 studies.4,7

    Incidence of Haematologic Toxicities

    Please find the incidence of haematologic toxicities with abemaciclib plus endocrine therapy in All Grade Haematologic Toxicities in the Abemaciclib Arms of the MONARCH Clinical Trials.

    All Grade Haematologic Toxicities in the Abemaciclib Arms of the MONARCH Clinical Trials7

    Event, %

    MONARCH 3
    N=327

    MONARCH 2
    N=441

    Neutropenia

    41

    46

    Anemia

    28

    29

    Thrombocytopenia

    10

    16

    Leukopenia

    21

    28

    Haematologic Toxicity of Special Interest - Neutropenia

    Across studies, neutropenia was observed within the first 2 months and did not resolve during the treatment. The neutropenia reversed in patients who discontinued the treatment.8

    Below you will find information about the incidence of neutropenia across the MonarchE, MONARCH 2, and MONARCH 3 studies. Please review the Verzenios Summary of Product Characteristics, particularly the section: 

    • 4.8 Undesirable effects 

    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 haematologic toxicities are shown in NCI CTCAE Grade Definitions.

    NCI CTCAE Grade Definitions9

    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.

    References

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

    2Crawford 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

    3Smith 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

    4Sledge 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

    5Goetz 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

    6Rugo 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. Accessed October 21, 2021. https://www.lillymedical.com/en-us/answers/management-of-abemaciclib-associated-adverse-events-in-patients-with-hr-her2-advanced-breast-cancer-analysis-of-the-monarch-trials-88694?hcpToken=A12DSa08bhrd123gg8

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

    8Rugo 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

    9US 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

    Links to references and third-party websites are provided solely for your convenience and to facilitate easy access to the sources cited.

    Date of Last Review: 15 October 2024

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