Verzenio® (Abemaciclib)

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Abemaciclib: MONARCH 3 - Use With NSAI in ABC

Abemaciclib demonstrates efficacy in combination with an NSAI with a PFS of 28.2 months in the abemaciclib arm vs 14.8 months in the placebo arm.

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The information contained in this letter may not completely match the current local labeling for ABEMACICLIB. Please see local labeling approved in your country. 

Background

MONARCH 3 was a randomized, double-blind, placebo-controlled, phase 3 study of abemaciclib or placebo with an NSAI (anastrozole or letrozole) in 493 postmenopausal women with HR+, HER2- advanced or MBC with no prior systemic treatment in this setting.1

Endocrine therapy in the neoadjuvant or adjuvant setting was permitted if patients had a disease free interval of >12 months since completion of ET.1

Patients were randomized 2:1 to abemaciclib or placebo in combination with an NSAI.

  • Abemaciclib 150 mg or matching placebo was administered orally twice daily on a continuous schedule.
  • Anastrozole 1 mg or letrozole 2.5 mg (per physician’s choice) was administered orally once daily on a continuous schedule.1

Patients were stratified according to metastatic site (visceral, bone-only, vs other) and prior (neo)adjuvant ET (AI, no ET, vs other). The primary endpoint was investigator-assessed PFS and key secondary endpoints included OS, response rates, and safety.1

Efficacy

Progression-free survival was evaluated according to RECIST version 1.1. At the time of the final PFS analysis, median follow-up was 26.7 months and OS data were immature.1,2 Median relative dose intensity was 85% for abemaciclib and 98% for placebo.2

Primary and Select Secondary Efficacy Endpoints in MONARCH 32

 

Abemaciclib + NSAI

Placebo + NSAI

Progression-free survivala

N=328

N=165

Median, months

28.2

14.8

Hazard ratio (95% CI)

0.540 (0.418, 0.698)

P value

.000002

Duration of responseb

n=163

n=61

Median, months

27.4

17.5

Best overall response for ITT population

N=328

N=165

Objective response rate, %c

49.7

37.0

Complete response, %

2.7

0.6

Clinical benefit rate, %d

78.0

71.5

Best overall response for patients With measurable disease

n=267

n=132

Objective response rate, %c

61.0e

45.5f

Complete response, %

3.4

0

Clinical benefit rate, %d

79.0

69.7

Abbreviations: ITT = intent-to-treat; NSAI = nonsteroidal aromatase inhibitor.

aInvestigator-assessed.

bResponder population.

cObjective response rate = complete response + partial response.

dClinical benefit rate = complete response + partial response + stable disease ≥6 months.

eConfirmed objective response rate = 55.4%.

fConfirmed objective response rate = 40.2%.

A blinded independent central review was conducted and confirmed ITT PFS benefit (HR=0.465; 95% CI: 0.339-0.636; p<.000001).2

Abemaciclib plus an NSAI demonstrated improved PFS across all patient subgroups analyzed.1-3

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, PR- tumors, and high-grade tumors.3

A subpopulation treatment effect pattern plot analysis of TFI of the MONARCH 3 patients who had received adjuvant ET demonstrated that patients who had a shorter TFI had a worse prognosis and received relatively greater benefit from abemaciclib plus NSAI than did patients with a longer TFI. Patients with bone-only disease or a longer TFI also received benefit from abemaciclib, but to a relatively lesser extent (HR ranging from approximately 0.6-0.8).3

Safety

Adverse Reactions in the MONARCH 3 Safety Population (abemaciclib+NSAI, n=327; placebo+NSAI, n=161)4

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.

In the abemaciclib arm, 13% of patients permanently discontinued treatment and dose reductions occurred in 43% of patients due to adverse reactions.5

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).1,2

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).1,2

Conclusion

Abemaciclib plus NSAI significantly improved PFS and ORR as initial therapy for HR+, HER2- postmenopausal advanced breast cancer patients compared with NSAI alone. Abemaciclib was generally well tolerated.1,2

References

1Goetz 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

2Johnston 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

3Di Leo A, O'Shaughnessy J, Sledge GW Jr, 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

4Verzenio [package insert]. Indianapolis, IN: Eli Lilly and Company; 2018.

5Data on file, Eli Lilly and Company and/or one of its subsidiaries.

Glossary

AE = adverse event

ALT = alanine aminotransferase 

ET = endocrine therapy

HER2- = human epidermal growth factor receptor 2-negative

HR = hazard ratio

HR+ = hormone receptor-positive

ITT = intent-to-treat

MBC = metastatic breast cancer

NSAI = nonsteroidal aromatase inhibitor

ORR = overall response rate

OS = overall survival

PFS = progression-free survival

RECIST = Response Evaluation Criteria in Solid Tumors

TFI = treatment-free interval

Fecha de la última revisión: 2019 M03 13


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