Source: European Medicines Agency (EU) Revision Year: 2024 Publisher: Eli Lilly Nederland B.V., Papendorpseweg 83, 3528BJ Utrecht, The Netherlands
Verzenios in combination with endocrine therapy is indicated for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive early breast cancer at high risk of recurrence (see section 5.1).
In pre- or perimenopausal women, aromatase inhibitor endocrine therapy should be combined with a luteinising hormone-releasing hormone (LHRH) agonist.
Verzenios is indicated for the treatment of women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer in combination with an aromatase inhibitor or fulvestrant as initial endocrine-based therapy, or in women who have received prior endocrine therapy.
In pre- or perimenopausal women, the endocrine therapy should be combined with a LHRH agonist.
Verzenios therapy should be initiated and supervised by physicians experienced in the use of anti-cancer therapies.
The recommended dose of abemaciclib is 150 mg twice daily when used in combination with endocrine therapy. Please refer to the summary of product characteristics of the endocrine therapy combination partner for the recommended posology.
Verzenios should be taken continuously for two years, or until disease recurrence or unacceptable toxicity occurs.
Verzenios should be taken continuously as long as the patient is deriving clinical benefit from therapy or until unacceptable toxicity occurs.
If a patient vomits or misses a dose of Verzenios, the patient should be instructed to take the next dose at its scheduled time; an additional dose should not be taken.
Management of some adverse reactions may require dose interruption and/or dose reduction as shown in Tables 1-7.
Table 1. Dose adjustment recommendations for adverse reactions:
| 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 2. Management recommendations for haematologic toxicities:
Complete blood counts should be monitored prior to the start of Verzenios 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) ≥1 500/mm³, platelets ≥100 000/mm³, and haemoglobin ≥8 g/dL are recommended.
| 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 – 1 500/mm³; Grade 2: ANC 1 000 - <1 500/mm³; Grade 3: ANC 500 - <1 000/mm³; Grade 4: ANC <500/mm³
LLN = lower limit of normal
Table 3. Management recommendations for diarrhoea:
Treatment with antidiarrhoeal agents, such as loperamide, should be started at the first sign of loose stools.
| Toxicitya | Management recommendations |
|---|---|
| Grade 1 | No dose adjustment required. |
| Grade 2 | If toxicity does not resolve within 24 hours to Grade 1 or less, suspend dose until resolution. Dose reduction is not required. |
| Grade 2 that persists or recurs after resuming the same dose despite maximal supportive measures | Suspend dose until toxicity resolves to Grade 1 or less. Resume at next lower dose. |
| Grade 3 or 4 or requires hospitalisation |
a NCI CTCAE
Table 4. Management recommendations for increased aminotransferases:
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be monitored prior to the start of Verzenios therapy, every two weeks for the first two months, monthly for the next two months, and as clinically indicated.
| Toxicitya | Management recommendations |
|---|---|
| Grade 1 (> ULN – 3.0 x ULN) Grade 2 (>3.0 – 5.0 x ULN) | No dose adjustment required. |
| Persistent or Recurrent Grade 2, or Grade 3 (>5.0 – 20.0 x ULN) | Suspend dose until toxicity resolves to baseline or Grade 1. Resume at next lower dose. |
| Elevation in AST and/or ALT >3 x ULN WITH total bilirubin >2 x ULN, in the absence of cholestasis | Discontinue abemaciclib. |
| Grade 4 (>20.0 x ULN) | Discontinue abemaciclib. |
a NCI CTCAE
ULN = upper limit of normal
Table 5. Management recommendations for interstitial lung disease (ILD)/pneumonitis:
| Toxicitya | Management recommendations |
|---|---|
| Grade 1 or 2 | No dose adjustment required. |
| Persistent or recurrent Grade 2 toxicity that does not resolve with maximal supportive measures within 7 days to baseline or Grade 1 | Suspend dose until toxicity resolves to baseline or Grade 1. Resume at next lower dose. |
| Grade 3 or 4 | Discontinue abemaciclib. |
a NCI CTCAE
Table 6. Management recommendations for venous thromboembolic events (VTEs):
| Toxicitya | Management recommendations |
|---|---|
| Early breast cancer | |
| All Grades (1, 2, 3, or 4) | Suspend dose and treat as clinically indicated. Abemaciclib may be resumed when the patient is clinically stable. |
| Advanced or metastatic breast cancer | |
| Grade 1 or 2 | No dose modification is required. |
| Grade 3 or 4 | Suspend dose and treat as clinically indicated. Abemaciclib may be resumed when the patient is clinically stable. |
a NCI CTCAE
Table 7. Management recommendations for non-haematologic toxicities (excluding diarrhoea, increased aminotransferases, and ILD/pneumonitis and VTEs):
| Toxicitya | Management recommendations |
|---|---|
| Grade 1 or 2 | No dose adjustment required. |
| Persistent or recurrent Grade 2 toxicity that does not resolve with maximal supportive measures to baseline or Grade 1 within 7 days | Suspend dose until toxicity resolves to Grade 1 or less. Resume at next lower dose. |
| Grade 3 or 4 |
a NCI CTCAE
Concomitant use of strong CYP3A4 inhibitors should be avoided. If strong CYP3A4 inhibitors cannot be avoided, the abemaciclib dose should be reduced to 100 mg twice daily.
In patients who have had their dose reduced to 100 mg abemaciclib twice daily and in whom co-administration of a strong CYP3A4 inhibitor cannot be avoided, the abemaciclib dose should be further reduced to 50 mg twice daily.
In patients who have had their dose reduced to 50 mg abemaciclib twice daily and in whom co-administration of a strong CYP3A4 inhibitor cannot be avoided, the abemaciclib dose may be continued with close monitoring of signs of toxicity. Alternatively, the abemaciclib dose may be reduced to 50 mg once daily or discontinued.
If the CYP3A4 inhibitor is discontinued, the abemaciclib dose should be increased to the dose used prior to the initiation of the CYP3A4 inhibitor (after 3 to 5 half-lives of the CYP3A4 inhibitor).
No dose adjustment is required based on age (see section 5.2).
No dose adjustments are necessary in patients with mild or moderate renal impairment. There are no data regarding abemaciclib administration in patients with severe renal impairment, end stage renal disease, or in patients on dialysis (see section 5.2). Abemaciclib should be administered with caution in patients with severe renal impairment, with close monitoring for signs of toxicity.
No dose adjustments are necessary in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment. In patients with severe (Child Pugh C) hepatic impairment, a decrease in dosing frequency to once daily is recommended (see section 5.2).
The safety and efficacy of abemaciclib in children and adolescents aged less than 18 years has not been established. No data are available.
Verzenios is for oral use.
The dose can be taken with or without food. It should not be taken with grapefruit or grapefruit juice (see section 4.5).
Patients should take the doses at approximately the same times every day.
The tablet should be swallowed whole (patients should not chew, crush, or split tablets before swallowing).
In the event of an abemaciclib overdose, fatigue and diarrhoea may occur. General supportive care should be provided.
3 years.
This medicinal product does not require any special storage conditions.
PCTFE/PE/PVC blisters sealed with an aluminium foil in packs of 14, 28, 42, 56, 70 or 168 film-coated tablets.
Aluminium/aluminium perforated unit dose blisters of 28 × 1 film-coated tablets.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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