Verzenios therapy should be initiated and supervised by physicians experienced in the use of anti-cancer therapies. Posology 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.
Duration of treatment Early breast cancer Verzenios should be taken continuously for two years, or until disease recurrence or unacceptable toxicity occurs. Advanced or metastatic breast cancer 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. Dose adjustments Management of some adverse reactions may require dose interruption and/or dose reduction as shown in Tables 1-7.
4 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 ≥ 1 00 000 / 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. Toxicity a 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 5 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.
0 x ULN) No dose adjustment required. 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.
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 6 Table 7. Management recommendations for non-haematologic toxicities (excluding diarrhoea, increased aminotransferases, and ILD/pneumonitis and VTEs) Toxicity a 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 CYP3A4 inhibitors 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 […]