Verzenios ® (abemaciklib)

För fullständig produktresumé för Verzenios se FASS.

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Verzenios® ▼ (abemaciclib): Användning hos patienter med levermetastaser

Verzenios (abemaciclib) var ett effektivt behandlingsalternativ för patienter med HR+, HER2-bröstcancer som har levermetastaser.

Detailed Information

The liver is a common site of metastatic spread in breast cancer and has been associated with a poor prognosis. 1,2

The pivotal study MONARCH 2 tested Verzenios in combination with fulvestrant, the pivotal study MONARCH 3 tested Verzenios in combination with aromatase inhibitors.3

An exploratory subgroup analysis was conducted in patients with liver metastases at baseline across pivotal studies in patients with HR+, HER2- advanced or metastatic breast cancer. The results of this analysis suggest that abemaciclib was an effective treatment option in patients with breast cancer who have liver metastases.1,2

Efficacy results of MONARCH 2 and MONARCH 3 are summarized in Table 1.  MONARCH 2 and MONARCH 3 PFS and Response Rates in Patients with Liver Metastases   Tolerability results for abemaciclib were generally consistent with the safety populations previously reported for each study.1,2

Table 1.  MONARCH 2 and MONARCH 3 PFS and Response Rates in Patients with Liver Metastases1,2,4

 

MONARCH 2

MONARCH 2

MONARCH 3

MONARCH 3

Endpoint

Abemaciclib + Fulvestrant

n=111

Placebo + Fulvestrant

n=59

Abemaciclib + NSAI

n=47

Placebo + NSAI

n=30

Median PFS, months

11.64

3.09

15.02

7.23

HR (95% CI)

0.447 (0.311, 0.644)

--

0.477 (0.272, 0.837)

--

ORRab, %

48.6

15.3

57.4

20.0

DCRac, %

76.6

49.2

85.1

63.3

CBRad, %

68.5

35.6

66.0

43.3

Abbreviations: CBR = clinical benefit rate; CR = complete response; DCR = disease control rate; HR = hazard ratio; NA = not applicable; NSAI = nonsteroidal aromatase inhibitor; ORR = objective response rate; PFS = progression-free survival; PR = partial response; SD = stable disease.

a With measurable disease.

b ORR = CR + PR.

c DCR = CR + PR + SD.

d CBR = CR + PR + SD ≥ 6 months.

While all subpopulations benefited from the addition of abemaciclib to ET regardless of prognosis, in a subgroup analysis of patients in MONARCH 2 and MONARCH 3, substantial benefit of abemaciclib (characterized by large increases in PFS [HRs = 0.4 - 0.5] and ORR [>30%]) was observed in poor prognosis subgroups with liver metastases, progesterone receptor-negative tumors, and high-grade tumors. 2,5

No dose adjustments are necessary in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment.3 

In patients with severe (Child Pugh C) hepatic impairment, a decrease in dosing frequency to once daily is recommended.3

Increases in ALT and AST were reported in patients receiving abemaciclib. 3

Based on the level of ALT or AST elevation, abemaciclib may require dose modification.3

Real World Evidence

A retrospective analysis of US EHR data from Vector Oncology’s data warehouse examined OS and patient characteristics in order to determine common poor prognostic factors. Data was collected from the initiation of therapy for first, second, and third lines of therapy.6

Of 378 women starting a first line of therapy, 17.2% and 39.2% of patients experienced an OS event prior to starting second or third lines of therapy, respectively. Patients with liver metastases were generally younger (mean age 57.2; SD 13.8 vs 61.2, 13.1; p=.016) and more likely to have a grade 3 tumor (36.1% vs 24.7%, p=.039). Higher mortality was also observed in patients with liver metastases across lines of therapy, with OS of 66.2% vs 56.9% with the first line of therapy. Sample size and selection criteria may limit generalizability of these results.6

Liver metastases positive patients had a poorer prognosis as they were more likely to have an OS event across  first to third line compared to liver metastases negative patients. For all 3 lines, median OS for liver metastases positive was shorter than the liver metastases negative median OS.6

Median OS in first line was 14 months shorter in liver metastases positive patients compared to liver metastases negative patients. Other potential indicators of poor prognosis, such as high tumor grade, are being explored.6

References

1. Di Leo A, Dickler M, Sledge GW Jr, et al. Efficacy and safety of abemaciclib in patients with liver metastases in the MONARCH 1, 2, and 3 studies. Poster presented at: 40th Annual San Antonio Breast Cancer Symposium (SABCS); December 5-9, 2017; San Antonio, TX.

2. Di Leo A, Dickler M, Sledge GW, et al. Efficacy and safety of abemaciclib in patients with liver metastases in the MONARCH 1, 2, and 3 studies [abstract]. Cancer Res. 2018:(78) (4 Suppl). http://dx.doi.org/10.1158/1538-7445.SABCS17-P5-21-02

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

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

5. Di Leo A, O'Shaughnessy J, Sledge GW, et al. Prognostic characteristics in hormone receptor-positive advanced breast cancer and characterization of abemaciclib efficacy [published online December 18, 2018]. NPJ Breast Cancer. 2018;4(1):41. http://dx.doi.org/10.1038/s41523-018-0094-2

6. Saverno K, Cuyan Carter G, Dufour R, et al. Outcomes among metastatic breast cancer patients with characteristics that confer a less favorable prognosis. Poster presented at: 41st Annual San Antonio Breast Cancer Symposium (SABCS); December 4-8, 2018; San Antonio, TX. https://www.abstracts2view.com/sabcs18/view.php?nu=SABCS18L_879&terms=

Glossary

CBR = clinical benefit ratio

CR = complete response

DCR = disease control rate

EHR = electronic healthcare record

ET = endocrine therapy

HER2- = human epidermal growth factor receptor 2-negative

HR = hazard ratio

HR+ = hormone receptor-positive

NSAI = nonsteroidal aromatase inhibitor

ORR = objective response rate

PFS = progression-free survival

PR = partial response

SD = stable disease

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 M03 13

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