Verzenios ® (abemaciklib)

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Verzenios® ▼ (abemaciclib): MONARCH 2 - Användning i combination med fulvestrant i avancerad bröstcancer

Abemaciclib i kombination med fulvestrant demonstrerar effekt med en progressionsfri överlevnad på 16,4 månader i abemaciclib-armen jämfört med 9,3 månader i placebo-armen.

Results of the MONARCH 2 Trial

Efficacy

The median relative dose intensity was 97.7% for the abemaciclib arm and 99.8% for the placebo arm.1 Dose reductions due to an adverse reaction occurred in 43% of patients in the abemaciclib arm.2 Median follow-up was 47.7 months.3

The efficacy analysis is presented in Table 1 and Table 2.

Table 1. Investigator-Assessed Efficacy ITT Analysis in MONARCH 23

 

Abemaciclib + Fulvestrant

Placebo + Fulvestrant

Progression-free survival

N=446

N=223

Median, months

16.9

9.3

Hazard ratio (95% CI)

0.536 (0.445, 0.645) 

P value

<.001

Overall survival

N=446

N=223

Median, months

46.7

37.3

Hazard ratio (95% CI)

0.757 (0.606, 0.945)

P value

.01

Abbreviation: ITT = intent-to-treat.

Table 2.  Investigator-Assessed Objective Response ITT Analysis in MONARCH 22


Abemaciclib + Fulvestrant

Placebo + Fulvestrant

Objective response for ITT population

N=446

N=223

Objective response rate, %

35.2

16.1

Complete response, %

3.1

0.4

Clinical benefit rate, %

72.2

56.1

Objective response for patients with measurable disease

N=318

N=164

Objective response rate, %

48.1

21.3

Complete response, %

3.5

0

Clinical benefit rate, %

73.3

51.8

Abbreviation: ITT = intent-to-treat.

The median duration of response was 22.8 months in the abemaciclib arm vs 13.9 months in the placebo arm.1

Abemaciclib plus fulvestrant demonstrated improved PFS across all patient subgroups analyzed.2,4,5

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.4

Abemaciclib plus fulvestrant provided a statistically significant improvement in OS. The OS benefit was consistent across subgroups, including patients with poor prognostic factors such as visceral metastasis (HR=0.675) and primary ET resistance (HR=0.686).3

Safety

Adverse reactions in MONARCH 2 are presented in Table 3. Serious adverse events were reported in 22% of patients in the abemaciclib arm and 11% of patients in the placebo arm.2

Table 3. Adverse Reactions in the MONARCH 2 Safety Population (abemaciclib+fulvestrant, n=441; placebo+fulvestrant, n=223)6

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

  • diarrhoea

  • leukopenia

  • anemia

  • infections

Diarrhoea

Grade 3 diarrhoea occurred in 13% of patients in the abemaciclib arm and <1% of patients in the placebo arm. There were no instances of grade 4 diarrhoea in either treatment arm.1 Diarrhoea typically occurred during the first treatment cycle (median onset 6 days) and was effectively managed with dose adjustment and antidiarrhoeal medication.2

Neutropenia

Grade 3/4 neutropenia was 27% in the abemaciclib arm vs 2% in the placebo arm. Febrile neutropenia was reported in 6 patients in the abemaciclib arm. Of these cases, 1 patient was incorrectly coded, and 1 patient had febrile neutropenia post chemotherapy. Febrile neutropenia was not associated with severe infection.2

Conclusion

Abemaciclib at 150 mg twice daily on a continuous schedule in combination with fulvestrant significantly improved PFS, OS, and ORR compared with placebo plus fulvestrant and was generally well tolerated. Abemaciclib plus fulvestrant was an effective treatment for patients with HR+, HER2- advanced breast cancer whose disease progressed while they were receiving ET.2,3

Description of the Monarch 2 Trial

MONARCH 2 was a randomized, double-blind, placebo-controlled phase 3 study of fulvestrant with or without abemaciclib in women with HR+, HER2- advanced breast cancer whose disease progressed

  • while they were receiving neoadjuvant or adjuvant ET

  • less than or equal to 12 months after adjuvant ET, or

  • while receiving ET for advanced breast cancer.2

The primary endpoint was investigator-assessed PFS and key secondary endpoints include ORR, DoR, OS, CBR , and safety.2

Patients were randomized 2:1 to abemaciclib plus fulvestrant or placebo plus fulvestrant.

  • Abemaciclib was administered at 150 mg orally twice daily on a continuous schedule.

  • Fulvestrant was administered as a 500 mg IM injection on

    • days 1 and 15 of the first cycle, and

    • day 1 of subsequent cycles (every 28 days).2

At study initiation, patients in the abemaciclib arm received 200 mg twice daily. Following a review of safety data and dose reduction rates, the protocol was amended to reduce the starting dose to 150 mg for new patients and all patients who were receiving 200 mg underwent a mandatory dose reduction to 150 mg.2

Patients continued therapy until PD, death, or withdrawal and were stratified by metastatic site (visceral, bone only vs other) and ET resistance (primary resistance vs secondary resistance).2

References

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

2. 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.

3. Sledge GW Jr, Toi M, Neven P, et al. The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor–positive, ERBB2-negative breast cancer that progressed on endocrine therapy — MONARCH 2: A randomized clinical trial. [published online September 29, 2019]. JAMA Oncol. http://dx.doi.org/10.1001/jamaoncol.2019.4782

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

5. Grischke EM, Pivot X, Llombart-Cussac A, et al. Abemaciclib with fulvestrant in patients with HR+, HER2- advanced breast cancer (ABC) that exhibited primary or secondary resistance to prior endocrine therapy (ET). Poster presented at: Annual Meeting of the European Society for Medical Oncology (ESMO) European Cancer Congress (ECC); October 19-23, 2018; Munich, Germany. https://www.esmo.org/content/download/149891/2691140/file/EMSO-2018-Abstract-Book-partial-version.pdf

6. Verzenio [package insert]. Indianapolis, IN: Eli Lilly and Company; 2018.

Glossary

CBR = clinical benefit ratio

DoR = duration of response

ET = endocrine therapy

HER2- = human epidermal growth factor receptor 2-negative

HR+ = hormone receptor-positive

IM = intramuscular

ORR = objective response rate

OS = overall survival

PD = progressive disease

PFS = progression-free survival

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 2019 M09 24

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