Verzenio ® (abemaciclib) tablets

50mg, 100mg, 150mg, 200mg

This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.

VERZENIO® (abemaciclib): Effect of Food

Verzenio (abemaciclib) may be taken with or without food.

Detailed Information

Abemaciclib may be taken with or without food.1,2

  • A high-fat, high-calorie meal (approximately 800-1000 calories with 150 calories from protein, 250 calories from carbohydrate, and 500-600 calories from fat) administered to healthy subjects increased the AUC of abemaciclib plus its active metabolites by 9% and increased Cmax by 26%.1,2

  • The magnitude of the change was within the therapeutic window for abemaciclib. There was no difference in median tmax in the fed state compared to the fasted state for abemaciclib.1,2

The NCI provides additional dietary guidance for the management of diarrhea including foods or drinks to avoid.3

Abemaciclib is metabolized to several metabolites primarily by CYP P450 3A.4

  • Patients should not consume grapefruit products while on treatment with abemaciclib.4

Introduction

Abemaciclib is an orally administered inhibitor of CDK 4 and 6 and dosed on a continuous schedule.5

Diarrhea is a frequently associated AE that

  • is predictable and manageable with antidiarrheal medication

  • typically occurs within the first month of therapy, and

  • decreased over the duration of treatment.5

Grade 3 diarrhea was experienced by 9% to 20% of patients receiving abemaciclib in the MONARCH 1, 2, and 3 studies.5

Phase 2 Study of the Impact of Food on Tolerability of Abemaciclib

Overview

A randomized, open-label phase 2 study was conducted in 5 countries from December 2018 to April 2019 to evaluate the impact of food on the incidence of grade 3 or prolonged grade 2 diarrhea in patients receiving abemaciclib monotherapy 200 mg orally BID during the first 3 cycles of study treatment.5

Patients with HR+, HER2- MBC and ECOG PS of ≤1 who had progressed after prior anti-estrogen therapy for MBC and received prior treatment with >1 chemotherapy regiment for MBC, but were CDK 4/6 inhibitor naïve  were randomly assigned 1:1:1 to receive abemaciclib

  • with a meal (Arm 1, n=24)

  • in a modified fasted condition (defined as >1 hour before or >2 hours after a meal) (Arm 2, n=23), or

  • without regard to food (Arm 3, n=24).5

This study was descriptive and not powered to analyze differences between study arms.5

Primary study endpoints were

  • incidence of grade  ≥3 diarrhea;

  • incidence of grade 2 diarrhea lasting >7 days;

  • dose reductions, dose interruptions, treatment discontinuations due to diarrhea, and

  • use of antidiarrheal agents.5

Secondary endpoints included overall safety and PK analysis.5

A patient-held electronic diary was centrally monitored with real-time access for physicians to assess diarrhea events.5 The patient diary recorded daily information on

  • number of stools

  • diarrhea

  • loperamide use, and

  • timing of abemaciclib intake relative to meals.5

The mean compliance for e-diary completion was 95.7% for the overall population.5 Mean compliance with meal conditions was

  • 99.5% in Arm 1

  • 95.2% in Arm 2, and

  • not applicable for Arm 3.5

Efficacy Results

Patients received ≥3 cycles in

  • Arm 1, 83.3%,

  • Arm 2, 78.3%, and

  • Arm 3, 91.7%.5

Primary endpoints results during the first 3 treatment cycles are summarized in Table 1..

Table 1. Primary Endpoints During First 3 Treatment Cycles of Abemaciclib5

 

Arm 1

(n=24)

Arm 2

(n=23)

Arm 3

(n=24)

Overall

(n=71)

1 grade 2 diarrhea lasting >7 days, %

8.3

17.4

20.8

15.5

1 grade 3 diarrhea, %

4.2a

0

0

1.4

1 grade 4 diarrhea, %

0

0

0

0

1 dose reduction due to diarrhea, %

16.7

8.7

12.5

12.7

1 dose interruption due to diarrhea, %

16.7

4.3

8.3

9.9

Treatment discontinued due to diarrhea, %

0

0

0

0

Loperamide use, %

95.8

91.3

95.8

94.4

a Duration of grade 3 diarrhea was 1 day.

Safety Results

Overall, the most frequently reported grade 3/4 TEAEs related to treatment were

  • neutropenia (28.2%)

  • leukopenia (11.3%)

  • thrombocytopenia (7.0%)

  • fatigue (5.6%)

  • nausea (5.6%), and

  • lymphopenia (5.6%).5

Conclusion

Global compliance with e-diary completion and meal condition was >95%. High-grade diarrhea occurred at much lower incidence than previously reported and was of short duration. Diarrhea was predominantly low grade and managed with loperamide and dose modifications in all meal cohorts.5

Enclosed Prescribing Information

VERZENIO® (abemaciclib) tablets, for oral use, Lilly

References

The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).

1. Turner K, Chappell J, Aburub A, et al. Abemaciclib tablet formulation is bioequivalent to capsules [abstract]. Cancer Res. 2018:78(4)(suppl):P1-10-14. http://cancerres.aacrjournals.org/content/78/4_Supplement/P1-10-14.short

2. Turner K, Chappell J, Aburub A, et al. Abemaciclib tablet formulation is bioequivalent to capsules. Abstract and poster presented at: 40th Annual San Antonio Breast Cancer Symposium (SABCS); December 5-9, 2017; San Antonio, TX. Abstract P1-10-14. https://www.sabcs.org/Past-Meetings

3. National Cancer Institute. Eating hints: before, during, and after cancer treatment. NIH Publication No. 18-7157. https://www.cancer.gov/publications/patient-education/eating-hints. Updated January 2018. Accessed February 15, 2018.

4. Verzenio [package insert]. Indianapolis, IN: Eli Lilly and Company; 2019.

5. Lim E, Boyle F, Okera M, et al. The impact of food on tolerability of abemaciclib in patients with previously treated hormone receptor-positive, HER2-negative, metastatic breast cancer: an open-label, randomized phase 2 study. Poster presented at: 42nd Annual San Antonio Breast Cancer Symposium (SABCS); December 10-14, 2019; San Antonio, TX. https://www.abstractsonline.com/pp8/#!/7946/presentation/1539

Glossary

AE = adverse event

AUC = area under the curve

BID = twice daily

CDK = cyclin-dependent kinase

Cmax = maximum concentration

CYP = cytochrome P450

ECOG = Eastern Cooperative Oncology Group

HER2- = human epidermal growth factor receptor 2-negative

HR+ = hormone receptor-positive

MBC = metastatic breast cancer

NCI = National Cancer Institute

PK = pharmacokinetic(s)

PS = performance status

TEAE = treatment-emergent adverse event

tmax = time of Cmax

Date of Last Review: October 04, 2019

Contact Lilly

Call Us

If you need information about a Lilly product or want to report an Adverse Event or Product Complaint, you may call us.

Available Mon - Fri, 9am - 8pm ET

Or you can

Ask us a question Chat with us

Submit a Request

Visit Us @LillyMedical