Verzenios ® (abemaciklib)

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Verzenios® ▼ (abemaciclib): Hematologiska biverkningar

Neutropeni, anemi, trombocytopeni och leukopeni var de vanligaste rapporterade hematologiska biverkningarna i kliniska studier med abemaciklib.

Incidence of Hematologic Toxicities

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

Abbreviated abemaciclib hematologic toxicities are presented in Table 1.

Table 1. All Grade Hematologic Toxicities in the Abemaciclib Arms of the MONARCH Clinical Trials2

Event, %

MONARCH 3
N=327

MONARCH 2
N=441

MONARCH 1
N=132

Neutropenia

41

46

37

Anemia

28

29

25

Thrombocytopenia

21

28

21

Leukopenia

10

16

17

The median time

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

  • to resolution was 11 to 15 days.  1

Across studies, neutropenia is observed early in the treatment course, within the first 2 months, and maintained over the course of treatment. On central laboratory analysis, neutrophil count decrease from the baseline visit was observed and mean neutrophil counts generally remained stable at the later visits and were reversible once patients discontinued from treatment.2

Dose Modification for Hematologic Toxicities

Dose modification is recommended for patients who develop Grade 3 or 4 neutropenia.1

Dose modifications due to neutropenia are presented in Table 2.

Table 2. Dose Modifications Due to Neutropenia in the Abemaciclib Arms of the MONARCH Trials3

Dose Modification, %

MONARCH 3
N=327

MONARCH 2
N=441

MONARCH 1
N=132

Dose reductions

12.8

10.0

10.6

Dose suspensions

17.4

16.3

15.9

Discontinuations

2.8

1.6

0

Management Recommendations for Haematologic Toxicities

Monitor complete blood counts

  • prior to the start of abemaciclib therapy

  • every 2 weeks for the first 2 months

  • monthly for the next 2 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

Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop grade 3 or grade 4 neutropenia.2

Abemaciclib dose modification is recommended based on individual patient safety and tolerability. Management of adverse reactions may require dose interruption, dose delay, or dose reduction.2

Dose modifications for adverse reactions are presented in Table 3 and management of hematologic toxicities in Table 4.

Table 3.   Dose adjustment recommendations for adverse reactions 1


Verzenios dose

combination therapy

Recommended dose

150 mg twice daily

First dose adjustment

100 mg twice daily

Second dose adjustment

50 mg twice daily

Table 4.   Management recommendations for haematologic toxicities 1

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. Before treatment initiation, absolute neutrophil counts (ANC) ≥1500/mm3, platelets ≥100,000/mm3, and haemoglobin ≥8 g/dL are recommended.  1

Toxicitya, b

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.

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

  LLN = lower limit of normal

Growth Factor Support

Hematopoietic growth factors have been shown to reduce the duration and severity of neutropenia and the risk of febrile neutropenia.4 In the MONARCH 3, MONARCH 2, and MONARCH 1 studies, growth factors were permitted to be administered in accordance with the ASCO guidelines.2,4,5

  • In the MONARCH 3 study, hematopoietic growth factors were administered to 14 patients (4.3%) in the abemaciclib arm and 2 patients (1.2%) in the placebo arm.2

  • In the MONARCH 2 study, hematopoietic growth factors were administered to 31 patients (7.0%) in the abemaciclib arm and 2 patients (0.9%) in the placebo arm.5

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

References

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

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

3. Rugo HS, Sledge GW Jr, Johnston S, et al. The association of early toxicity and outcomes for patients treated with abemaciclib. Poster presented at: 54th Annual Meeting of the American Society of Clinical Oncology (ASCO); June 1-5, 2018; Chicago, IL. https://meetinglibrary.asco.org/record/161891/abstract.

4. 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. http://jco.ascopubs.org/content/early/2015/07/08/JCO.2015.62.3488.full.

5. Sledge GW, 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. http://dx.doi.org/10.1200/JCO.2017.73.7585.

Glossary

ANC = absolute neutrophil count

ASCO = American Society of Clinical Oncology

CTCAE = Common Terminology Criteria for Adverse Events

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.

Datum fӧr senaste ӧversyn 2018 M06 21

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