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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.
Can Verzenio® (abemaciclib) be taken with or without food?
Verzenio (abemaciclib) may be taken with or without food.
Effect of Food with Abemaciclib
- 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 area under the curve (AUC) of abemaciclib plus its active metabolites by 9% and increased maximum concentration (Cmax) by 26%.1,3
- The magnitude of the change was within the therapeutic window for abemaciclib. There was no difference in median time (tmax) of Cmax in the fed state compared to the fasted state for abemaciclib.1
The National Cancer Institute provides additional dietary guidance for the management of diarrhea including foods or drinks to avoid.4
Abemaciclib is metabolized to several metabolites primarily by cytochrome P450 3A4.5
- Patients should not consume grapefruit products while on treatment with abemaciclib.5
Introduction
Abemaciclib is an orally administered inhibitor of cyclin-dependent kinase (CDK) 4 and 6 and dosed twice daily on a continuous schedule.2
Diarrhea is a frequently associated adverse event that
- is predictable and manageable with antidiarrheal medication
- typically occurs within the first month of therapy, and
- decreased over the duration of treatment.6
Phase 2 Study of the Impact of Food on Tolerability of Abemaciclib in Patients with Advanced Breast Cancer
Overview
A global, randomized, open-label phase 2 study (NCT03703466) was conducted in 5 countries from December 2018 to April 2019 evaluating the timing of food intake on the incidence of severe diarrhea (grade ≥3) or prolonged grade 2 diarrhea (>7 days duration) when receiving abemaciclib monotherapy in 72 patients with previously treated hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC).2,7
Patients and Methods
Patients were randomized patients 1:1:1 to receive abemaciclib 200 mg monotherapy orally twice daily
- with a meal (Arm 1)
- in a modified fasted condition (defined as ≥1 hour before or ≥2 hours after a meal) (Arm 2), or
- without regard to food (Arm 3).2
This study was descriptive and not powered to analyze differences between study arms.2
The primary objective was to evaluate and summarize investigator-assessed
- incidence of grade ≥3 and prolonged grade 2 (>7 days duration) diarrhea
- dose reductions
- dose interruptions
- discontinuations due to diarrhea, and
- patient-reported utilization of anti-diarrhea medications during the first 3 cycles of treatment.2
A patient-held electronic diary was monitored by investigators. The patient diary recorded daily information on the timing of each abemaciclib does in relation to
- a meal
- number of bowel movements (BM), and
- number of loperamide tablets.2
Patients recorded daily number of BMs for a week prior to study commencement to determine an accurate baseline.2 The mean compliance for e-diary completion was 95.7% across all study arms.2
Demographics
A total of 72 patients were enrolled, with 24 patients randomized to each of the three arms. However, one patient in Arm 2 withdrew from the study and did not receive treatment, resulting in a safety population of 71 patients.2
presents the patient demographics and baseline characteristics in the intent-to-treat population.
|
Overall |
Arm 1a |
Arm 2b |
Arm 3c |
Sex, n (%) |
||||
Female |
71 (98.6) |
23 (95.8) |
24 (100.0) |
24 (100.0) |
Male |
1 (1.4) |
1 (4.2) |
0 |
0 |
Age categories, n (%) |
||||
<65 years |
53 (73.6) |
17 (70.8) |
15 (62.5) |
21 (87.5) |
≥65 years |
19 (26.4) |
7 (29.2) |
9 (37.5) |
3 (12.5) |
Age (years) |
||||
Mean |
57.6 |
58.2 |
56.9 |
57.6 |
Race, n (%) |
||||
Asian |
2 (2.8) |
2 (8.3) |
0 |
0 |
White |
70 (97.2) |
22 (91.7) |
24 (100.0) |
24 (100.0) |
BMI, kg/m2 (SD) |
||||
Mean |
26.9 (4.5) |
26.6 (4.3) |
28.3 (5.4) |
26.0 (3.6) |
Region, n (%) |
||||
Turkey/Russia |
21 (29.2) |
7 (29.2) |
7 (29.2) |
7 (29.2) |
Australia/Spain/Belgium |
51 (70.8) |
17 (70.8) |
17 (70.8) |
17 (70.8) |
ECOG PS, n (%)d |
||||
0 |
37 (51.4) |
13 (54.2) |
10 (41.7) |
14 (58.3) |
1 |
34 (47.2) |
11 (45.8) |
13 (54.2) |
10 (41.7) |
Nature of disease, n (%) |
||||
Visceral |
59 (81.9) |
20 (83.3) |
17 (70.8) |
22 (91.7) |
Bone only |
8 (11.1) |
3 (12.5) |
5 (20.8) |
0 |
Others |
4 (5.6) |
1 (4.2) |
1 (4.2) |
2 (8.3) |
Missing |
1 (1.4) |
0 |
1 (4.2) |
0 |
Number of organ sites (%) |
||||
1 |
14 (19.4) |
3 (12.5) |
8 (33.3) |
3 (12.5) |
2 |
24 (33.3) |
9 (37.5) |
5 (20.8) |
10 (41.7) |
≥3 |
33 (45.8) |
12 (50.0) |
10 (41.7) |
11 (45.8) |
Number of prior chemotherapy regimens for ABC, n (%) |
||||
<5 |
54 (75.0) |
20 (83.3) |
14 (60.9) |
20 (83.3) |
≥5 |
16 (22.2) |
4 (16.7) |
9 (39.1) |
3 (12.5) |
Abbreviations: ABC = advanced breast cancer; BMI = body mass index; ECOG = Eastern Cooperative Oncology Group; N = number of patients in the intent-to-treat population; n = number of patients within category; PS = performance status.
aAll arms received 200 mg abemaciclib monotherapy twice per day: Arm 1=taken with a meal.
bAll arms received 200 mg abemaciclib monotherapy twice per day: Arm 2=taken without a meal (modified fasting condition).
cAll arms received 200 mg abemaciclib monotherapy twice per day: Arm 3=taken without regard to food.
dECOG status missing for 1 patient in Arm 2.
Results
The incidence of investigator-assessed diarrhea or dose modifications did not appear to be impacted by food. Although low, the incidence of prolonged grade 2 and grade 3 diarrhea over the first three cycles of treatment was comparable across all three arms as seen in .2
It was notable that investigator assessed grade 3 diarrhea only occurred in 1 patient overall (1.4%) during cycle 1 in Arm 1 and lasted 1 day. Overall, 11 patients (15.5%) had grade 2 diarrhea that persisted for >7 days.2
Dose reductions and omissions (dose interruptions) were balanced across Arms 1, 2, and 3 with 9 (12.7%) of all 71 patients having at least 1 dose reduction due to diarrhea and 7 (9.9%) of all patients requiring a dose omission for diarrhea as seen in .2
Loperamide was used at least once by 94% of the patients in the first 3 cycles. No patient experienced grade 3 or greater constipation despite the frequent use of loperamide.2
According to both investigator assessment (1 patient in Arm 1) and patient-reported assessment (1 patient each in Arms 1 and 3), the median duration of grade 3 diarrhea was 1 day. The investigator-assessed median duration of grade 2 diarrhea was 2 days overall. No patient discontinued treatment due to diarrhea, however, 9 patients (12.7%) had a dose reduction, and 7 patients (9.9%) had a dose omission due to diarrhea.2
Overall, 91.5% of the population experienced Investigator-reported treatment-emergent adverse events (TEAEs) of diarrhea ().2
There were no grade 4 or grade 5 diarrhea events reported.2
|
Overalla |
Arm 1b |
Arm 3e |
|
Endpoint |
|
|
|
|
Diarrhea |
||||
Any grade, n (%) |
65 (91.5) |
21 (87.5) |
22 (95.7) |
22 (91.7) |
Grade 1, n (%) |
35 (49.3) |
10 (41.7) |
14 (60.9) |
11 (45.8) |
Duration, median days |
8 |
9 |
6 |
10 |
Grade 2, n (%) |
29 (40.8) |
10 (41.7) |
8 (34.8) |
11 (45.8) |
Duration, median days |
2 |
2 |
7 |
3 |
Lasting >7 days, n (%) |
11 (15.5) |
2 (8.3) |
4 (17.4) |
5 (20.8) |
Grade 3, n (%) |
1 (1.4) |
1 (4.2) |
0 |
0 |
Duration, median days |
1 |
1 |
0 |
0 |
Dose modification due to diarrhea, n (%) |
||||
≥1 dose reduction |
9 (12.7) |
4 (16.7) |
2 (8.7) |
3 (12.5) |
≥1 dose omission |
7 (9.9) |
4 (16.7) |
1 (4.3) |
2 (8.3) |
Treatment discontinued |
0 |
0 |
0 |
0 |
Loperamide use, n (%) |
67 (94.3) |
23 (95.8) |
21 (91.3) |
23 (95.8) |
Abbreviations: N = number of patients receiving at least 1 abemaciclib dose (safety population); n = number of patients within category.
aOne patient in Arm 2 withdrew from the study and did not receive treatment, resulting in a safety population of 71 patients.
bAll arms received 200 mg abemaciclib monotherapy twice per day: Arm 1=taken with a meal. First three treatment cycles only.
cOne patient in Arm 2 discontinued from the study prior to receiving treatment.
dAll arms received 200 mg abemaciclib monotherapy twice per day: Arm 2=taken without a meal (modified fasting condition). First three treatment cycles only.
eAll arms received 200 mg abemaciclib monotherapy twice per day: Arm 3=taken without regard to food. First three treatment cycles only.
During the first 3 cycles, no patients experienced a serious adverse event of diarrhea or discontinued abemaciclib due to diarrhea.2
|
Overalla |
Arm 1b |
Arm 2c |
Arm 3d |
TEAE, n (%)e |
|
|
|
|
Neutropenia |
20 (28.2) |
7 (29.2) |
3 (13.0) |
10 (41.7) |
Leukopenia |
9 (12.7) |
5 (20.8) |
0 |
4 (16.7) |
Thrombocytopenia |
6 (8.5) |
4 (16.7) |
1 (4.3) |
1 (4.2) |
Nausea |
4 (5.6) |
1 (4.2) |
3 (13.0) |
0 |
Anemia |
6 (8.5) |
3 (12.5) |
1 (4.3) |
2 (8.3) |
Lymphopenia |
4 (5.6) |
3 (12.5) |
1 (4.3) |
0 |
AST increased |
4 (5.6) |
3 (12.5) |
1 (4.3) |
0 |
ALT increased |
2 (2.8) |
2 (8.3) |
0 |
0 |
Vomiting |
3 (4.2) |
1 (4.2) |
2 (8.7) |
0 |
Fatigue |
4 (5.6) |
1 (4.2) |
2 (8.7) |
1 (4.2) |
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; N = number of patients receiving at least one abemaciclib dose (safety population); n = number of patients within category; TEAE = treatment-emergent adverse event.
aOne patient in Arm 2 withdrew from the study and did not receive treatment, resulting in a safety population of 71 patients.
bAll arms received 200 mg abemaciclib monotherapy twice per day: Arm 1=taken with a meal. First three treatment cycles only.
cAll arms received 200 mg abemaciclib monotherapy twice per day: Arm 2=taken without a meal (modified fasting condition). First three treatment cycles only.
dAll arms received 200 mg abemaciclib monotherapy twice per day: Arm 3=taken without regard to food. First three treatment cycles only.
eOne patient in treatment Arm 1 died due to respiratory failure and one patient in Arm 2 died due to abnormal hepatic function; neither death was considered related to the study treatment.
Conclusion
The results suggest that the timing of food intake was not related to abemaciclib-associated diarrhea, and was
- predominantly low grade
- of short duration, and
- well managed with loperamide and dose modifications.2
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Turner P, Chappell J, Aburub A, et al. Abemaciclib tablet formulation is bioequivalent to capsules. Cancer Res. 2018;78(4 suppl):P1-10-14. American Association for Cancer Research abstract P1-10-14. http://dx.doi.org/10.1158/1538-7445.Sabcs17-p1-10-14
2Lim E, Boyle F, Okera M, et al. An open label, randomized phase 2 trial assessing the impact of food on the tolerability of abemaciclib in patients with advanced breast cancer. Breast Cancer Res Treat. Published online August 1, 2022. https://doi.org/10.1007/s10549-022-06690-5
3Turner 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
4Eating hints: before, during, and after cancer treatment. National Cancer Institute. October 17, 2014. Updated January 2018. Accessed August 9, 2022. https://www.cancer.gov/publications/patient-education/eating-hints
5Verzenio [package insert]. Indianapolis, IN: Eli Lilly and Company; 2021.
6Lim 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. Accessed May 4, 2021. https://www.abstractsonline.com/pp8/#!/7946/presentation/1539
7A study of abemaciclib (LY2835219) with and without food in participants with metastatic breast cancer. ClinicalTrials.gov identifier: NCT03703466. Updated August 10, 2022. Accessed August 17, 2022. https://clinicaltrials.gov/ct2/show/NCT03703466
Date of Last Review: August 17, 2022