Verzenios ® (abemaciklib)

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Verzenios® ▼ (abemaciclib): Vanligaste Biverkningar

De vanligaste biverkningarna är diarré, utmattning, neutropeni och illamående.

Abemaciclib in Combination With Nonsteroidal Aromatase Inhibitor (NSAI) (MONARCH 3)

Adverse reactions in MONARCH 3 are presented in Table 1. Serious adverse events were reported in 31% of patients in the abemaciclib arm and 17% of patients in the placebo arm.1

Table 1. Adverse Reactions in the MONARCH 3 Safety Population (abemaciclib+NSAI, n=327; placebo+NSAI, n=161)2

All grade adverse reactions reported in ≥20% of patients

Grade 3 or 4 adverse reactions reported in ≥5% of patients

  • diarrhea

  • neutropenia

  • nausea

  • infections

  • abdominal pain

  • fatigue

  • anemia

  • vomiting

  • alopecia

  • decreased appetite

  • leukopenia

  • neutropenia

  • alanine aminotransferase increased

  • diarrhea

  • leukopenia

  • anemia

Abbreviation: NSAI = nonsteroidal aromatase inhibitor.

Deaths due to AEs were reported in 11 patients in the abemaciclib arm and included

  • lung infection (n=4)

  • embolism (n=2)

  • respiratory failure (n=2)

  • cerebral ischemia (n=1)

  • cerebrovascular accident (n=1), and

  • pneumonitis (n=1).3,4

Deaths due to AEs were reported in 2 patients in the placebo arm and included

  • general physical health deterioration (n=1), and

  • sudden death (n=1).3,4

Abemaciclib in Combination With Fulvestrant (MONARCH 2)

Adverse reactions in MONARCH 2 are presented in Table 2. Serious adverse events were reported in 22% of patients in the abemaciclib arm and 11% of patients in the placebo arm.5

Table 2. Adverse Reactions in the MONARCH 2 Safety Population (abemaciclib+fulvestrant, n=441; placebo+fulvestrant, n=223)2

All grade adverse reactions reported in ≥20% of patients

Grade 3 or 4 adverse reactions reported in ≥5% of patients 

  • diarrhoea

  • fatigue

  • neutropenia

  • nausea

  • infections

  • abdominal pain

  • anemia

  • leukopenia

  • decreased appetite

  • vomiting

  • headache

  • neutropenia

  • diarrhea

  • leukopenia

  • anemia

  • infections

Deaths during treatment or during the 30-day follow-up were reported in

  • 14 patients (3%) in the abemaciclib arm, and

  • 10 patients (5%) in the placebo arm.5

Deaths due to AEs were reported in

  • 9 patients in the abemaciclib arm, and

  • 2 patients in the placebo arm.5

Deaths deemed by the investigators to be related to abemaciclib treatment were reported in

  • 2 patients with sepsis in whom guidance regarding GCSFs administration and dose reduction was not followed, and

  • 1 patient with viral pneumonia receiving steroids for spinal stenosis.5

Additionally, 2 deaths (0.5%) due to pneumonitis were reported in patients receiving abemaciclib plus fulvestrant.2

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.  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.  Febrile neutropenia was reported in 0.9% patients. Dose modification is recommended for patients who develop Grade 3 or 4 neutropenia.2

Diarrhoea

Diarrhoea was the most commonly reported adverse reaction. Incidence was greatest during the first month of abemaciclib treatment and was lower subsequently. The median time to onset of the first diarrhoea event was approximately 6 to 8 days across studies, and the median duration of diarrhoea was 9 to 12 days (Grade 2) and 6 to 8 days (Grade 3) across studies. Diarrhoea returned to baseline or lesser grade with supportive treatment such as loperamide and/or dose adjustment.2

Increased Aminotransferases

In patients receiving abemaciclib in combination with aromatase inhibitors or fulvestrant, ALT and AST elevations were reported frequently (15.1% and 14.2%, respectively). 2

Grade 3 or 4 ALT or AST elevations (based on laboratory findings) were reported in 6.1% and 4.2% patients. The median time to onset of Grade 3 or 4 ALT elevation was 57 to 61 days, and median time to resolution was 14 days. The median time to onset of Grade 3 or 4 AST elevation was 71 to 185 days, and median time to resolution was 13 to 15 days.2 

Dose modification is recommended for patients who develop Grade 3 or 4 ALT or AST increase.2

Increases in Serum Creatinine

Although not an adverse reaction, abemaciclib has been shown to increase serum creatinine in

  • 98.3% of patients (based on laboratory findings),

  • 1.9% Grade 3 or 4 (based on laboratory findings).2 

In patients receiving an aromatase inhibitor or fulvestrant alone, 78.4% reported an increase in serum creatinine (all laboratory grades).2 

Abemaciclib has been shown to increase serum creatinine due to inhibition of renal tubular secretion transporters without affecting glomerular function (as measured by iohexol clearance).2

 In clinical studies, increases in serum creatinine occurred

  • within the first month of abemaciclib dosing,

  • remained elevated but stable through the treatment period,

  • were reversible upon treatment discontinuation,

and were not accompanied by changes in markers of renal function, such as blood urea nitrogen (BUN), cystatin C, or calculated glomerular filtration rate based on cystatin C.2

References

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

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

3. Goetz 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.

4. Johnston S, Martin M, Di Leo A, et al. MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. NPJ Breast Cancer. 2019;5:5. http://dx.doi.org/10.1038/s41523-018-0097-z

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

AE = adverse event

ALT = alanine aminotransferase 

AST = aspartate aminotransferase

BUN = blood urea nitrogen

GCSF = granulocyte colony stimulating factor

NSAI = nonsteroidal aromatase inhibitor

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 M07 29

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