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Drug Trials Snapshot: VERZENIO

 

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
 

LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to the VERZENIO Package Insert for complete information.

VERZENIO (abemaciclib)

(ver-ZEN-ee-oh)
Eli Lilly and Company
Approval date:September 28, 2017


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

VERZENIO is a drug for treatment of a specific form of breast cancer called hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer.
VERZENIO is used in combination with fulvestrant (another drug used to treat breast cancer) when the breast cancer worsened after hormonal therapy.
VERZENIO is taken alone when the breast cancer worsened after hormonal therapy and chemotherapy.
 

How is this drug used?

VERZENIO tablet of 150 mg is taken twice daily in combination with fulvestrant . VERZENIO tablet of 200 mg is taken twice daily when used alone.

What are the benefits of this drug?

The first trial measured the length of time tumors did not grow after treatment (progression-free survival). The progression-free survival for patients taking VERZENIO with fulvestrant was about 16 months compared to 9 months for patients taking a placebo with fulvestrant.
The second trial measured the percent of patients whose tumors completely or partially shrank after treatment (objective response rate). In the trial, approximately 20 percent of patients taking VERZENIO experienced complete or partial shrinkage of their tumors that lasted about 9 months.

What are the benefits of this drug (results of trials used to assess efficacy)?

Table 2 shows  efficacy results  for Trial 1 in patients with disease progression following endocrine therapy where VERZENIO was used in combination with fulvestrant.

 VERZENIO plus FulvestrantPlacebo plus Fulvestrant
Progression-Free SurvivalN=446N=223
Number of patients with an event (n, %)222 (49.8)157 (70.4)
Median (months, 95% CI)16.4 (14.4, 19.3)9.3 (7.4, 12.7)
Treatment effect (months)7.2
Hazard ratio (95% CI) and p-value0.553 (0.449, 0.681)
p-valuep<>
Objective Response for Patients with Measurable DiseaseN=318N=164
Objective response ratea (n, %), 95% CI153 (48.1)35 (21.3)
95% CI42.6, 53.615.1, 27.6
Complete response, n (%)11 (3.5)0
Partial response, n (%)142 (44.7)35 (21.3)

Abbreviations: CI = confidence interval.
aComplete response + partial response.

VERZENIO Prescribing Information

Table 3 summarizes efficacy results for Trial 2 in patients with disease progression following endocrine therapy and 1-2 chemotherapy regimens where VERZENIO was used as monotherapy.

Table 3. Efficacy Results – Trial 2

 VERZENIO 200 mg
N=132
Investigator AssessedIndependent Review
Objective Response Ratea, n (%)26 (19.7)23 (17.4)
95% CI (%)13.3, 27.511.4, 25.0
Median Time to Response3.7 months4.0 months
Range1.1-14.2 months1.7-9.9 months
Median Duration of Response8.6 months7.2 months
95% CI (%)5.8, 10.25.6, NR
Clinical Benefit Rateb, n (%)56 (42.4)50 (37.9)
95% CI (%)(33.9, 51.3)(29.6, 46.7)

Abbreviations: CI = confidence interval, NR = not reached.
aAll responses were partial responses.
bClinical benefit rate includes all patients who achieved an objective response or who had stable disease for at least 6 months.

 VERZENIO Prescribing Information

Were there any differences in how well the drug worked in clinical trials among sex, race and age?


  • Sex:  The trial included only women therefore sex differences cannot be determined.
  • Race:  The majority of patients were white. The number of patients in other races was limited; therefore, differences in response among races could not be determined.
  • Age:  VERZENIO worked similarly in patients above and below 65 years of age.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

Table 4 shows the efficacy results by relevant demographic and geographic subgroups

Table 4. Progression-Free Survival by Subgroup Analysis-Trial 1

 NHR95% CI
Age
< 65="" years="">4240.520.40, 0.67
>= 65 Years old2450.630.45, 0.87
Race
White3730.630.48, 0.82
Asian2140.510.35, 0.73
Other820.430.21, 0.85
Region
USA1210.680.42, 1.09
Rest of World5480.530.42, 0.66

HR=hazard ratio; CI=confidence interval

FDA Review

Table 5. Overall Response Rate by Subgroup Analysis-Trial 2

 NORR95% CI
Age
< 65="" years="">9023.3%15.0, 33.4
>= 65 Years old4211.9%4.0, 25.6
Race
White11219.6%12.7, 28.2
Other825%3.2, 65.1
Region
USA7021.4%12.5, 32.8
Rest of World6217.7%12.0, 33.7

ORR=overall response rate; CI=confidence interval

FDA Review

What are the possible side effects?

VERZENIO may cause serious side effects, including severe diarrhea, low white blood cell counts (neutropenia), liver damage and blood clots in veins and lungs.

The most common side effects include diarrhea, nausea, abdominal pain, infections, tiredness, low blood counts, decreased appetite, vomiting, and headache.

What are the possible side effects (results of trials used to assess safety)?

Tables 6 and 7 below summarize common adverse reactions at all grades of severity that occurred in Trials 1 and 2, respectively.

Table 6. Adverse Reactions (≥10% of Patients Receiving VERZENIO Plus Fulvestrant) in Trial 1a

 VERZENIO plus Fulvestrant N=441Placebo plus Fulvestrant N=223
Adverse Reactions (MedDRA) System Organ ClassAll Grades %Grade 3 %Grade 4 %All Grades %Grade 3 %Grade 4 %
Gastrointestinal Disorders
Diarrhea86.413.4024.70.40
Nausea45.12.7022.90.90
Vomiting25.90.9010.31.80
General Disorders and Administration Site Conditions
Fatigueb39.92.7026.90.40
Blood and Lymphatic System Disorders
Neutropeniac46.023.62.94.01.30.4
Anemiad29.07.00.23.60.90
Leukopeniae28.38.60.21.800
Thrombocytopeniaf15.62.01.42.700.4
Investigations
Alanine aminotransferase increased13.43.90.25.41.80
Aspartate aminotransferase increased12.22.306.72.70
Skin and Subcutaneous Tissue Disorders
Alopecia15.6001.800

aBefore a study amendment changed the starting dose to 150 mg, 121 of the 446 ITT patients (27%) initially received a 200 mg starting dose. Median duration for 200 mg dosing was 34 days.

Consolidated event terms include the following:
bAsthenia, Fatigue.
cNeutropenia, Neutrophil count decreased.
dAnemia, Hematocrit decreased, Hemoglobin decreased, Red blood cell count decreased.
eLeukopenia, White blood cell count decreased.
fPlatelet count decreased, Thrombocytopenia.

 VERZENIO Prescribing Information

Table 7. Adverse Reactions (≥10% of Patients) in Trial 2

 VERZENIO N=132
Adverse Reactions (MedDRA) System Organ ClassAll Grades %Grade 1 %Grade 2 %Grade 3 %Grade 4 %
Gastrointestinal Disorders
Diarrhea90.241.728.819.70
Nausea64.439.420.54.50
Vomiting34.822.710.61.50
Dry mouth13.612.11.500
Stomatitis13.611.42.300
General Disorders and Administration Site Conditions
Fatiguea65.221.231.112.90
Blood and Lymphatic System Disorders
Neutropeniab37.11.511.418.95.3
Anemiac25.08.312.14.50
Thrombocytopeniad20.59.86.83.80
Leukopeniae17.42.39.15.30.8
Metabolism and Nutrition Disorders
Decreased appetite45.528.014.43.00
Nervous System Disorders
Dysgeusia12.110.61.500
Skin and Subcutaneous Tissue Disorders
Alopecia12.19.82.300

Consolidated event terms include the following:
aAsthenia, Fatigue.
bNeutropenia, Neutrophil count decreased.
cAnemia, Hematocrit decreased, Hemoglobin decreased, Red blood cell count decreased.
dPlatelet count decreased, Thrombocytopenia.
eLeukopenia, White blood cell count decreased.

 VERZENIO Prescribing Information

Were there any differences in side effects among sex, race and age?

  • Sex:  The trial included only women therefore sex differences cannot be determined.
  • Race: The majority of patients were white. The number of patients in other races was limited; therefore, differences in side effects among races could not be determined.
  • Age:  The incidence of overall side effects was similar in patients above and below 65 years of age.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

Analysis of the two most common adverse reactions by age and race subgroups in Trial 1 is presented in Tables 8 and 9.  Subgroup analysis for Trial 2 was limited to age only due to the small sample size of race subgroups.

Table 8. Summary of Adverse Reactions by Age -Trial 1

 < 65="">≥ 65 years
Adverse ReactionVERZENIO
plus fulvestrant,
N=287
Placebo
plus fulvestrant,
N=133
VERZENIO
plus fulvestrant,
N=154
Placebo
plus fulvestrant,
N=90
Diarrhea249 (86.8)27 (20.3)132 (85.7)28 (31.1)
Nausea117 (40.8)29 (21.8)82 (53.2)22 (24.4)

Table 9. Summary of Adverse Reactions by Race -Trial 1

 WhiteAsian
Adverse ReactionVERZENIO
plus fulvestrant,
N=234
Placebo
plus fulvestrant,
N=136
VERZENIO
plus fulvestrant,
N=148
Placebo
plus fulvestrant,
N=65
Diarrhea200 (85.5)38 (27.9)134 (90.5)13 (20.0)
Nausea121 (51.7)36 (26.5)56 (37.8)11 (16.9)

Table 10. Summary of Adverse Reactions by Age -Trial 2

Adverse Reaction< 65="">≥ 65 years
VERZENIO
N=90
VERZENIO
N=42
Diarrhea82 (91.1)37 (88.1)
Nausea57 (63.3)28 (66.7)

Clinical trial report

Who participated in the clinical trials?

The FDA approved VERZENIO based on evidence from two clinical trials that enrolled women with HR-positive, HER2-negative advanced breast cancer.

Patients in Trial 1 (NCT02107703) had an advanced  breast cancer that progresed  after hormone therapy. The trial was conducted at 145 sites in North America, Europe and Asia.

Patients in Trial  2 (NCT 02102490) had an advanced  breast cancer that progresed  after hormone  and chemo therapy . The trial was conducted at 35 sites in US and Europe.

Figures 1a and 1b summarizes how many women were in the clinical trials.

Figure 1a. Baseline Demographics by Sex-Trial 1

Pie chart summarizing  669 women (100%) who participated in the clinical trial 1.

Figure 1b. Baseline Demographics by Sex-Trial 2

Pie chart summarizing  132 women (100%) who participated in the clinical trial 2.

FDA Review

Figures 2a and 2b and Table 1 summarize patients by race in the clinical trials.

Figure 2a. Baseline Demographics by Race-Trial 1

Pie chart summarizing the percentage of patients by race in the clinical trial 1. In total, 373 White (56%), 214 Asian (32%), 14 Black or African Americans (2%) 26 American Indian or Alaska Native (4%) and 42 Other (6%), participated in the clinical trial.

Figure 2b. Baseline Demographics by Race-Trial 2

Pie chart summarizing the percentage of patients by race in the clinical trial 2. In total, 112 White (85%), 2 Asian (1%), 6 Black or African Americans (5%) and 12 patients with missing race data (9%) participated in the clinical trial.

Table 1. Demographics by Race (Trials 1 and 2)

RaceTrial 1Trial 2
Number of PatientsPercentageNumber of PatientsPercentage
White3735611285
Asian2143221
Black or African American14265
American Indian or Alaska Native26400
Multiple2less than 100
Missing*406129

FDA Review


 

 

Figure 3a. Baseline Demographics by Age-Trial 1

Pie chart summarizing how many individuals of certain age groups were in the clinical trial 1. In total, 424 patients were younger than 65 years (63%), 174 were 65-74 years old (26%), and  71  patients were  75 years and older (11 %).

Figure 3b. Baseline Demographics by Age-Trial 2

Pie chart summarizing how many individuals of certain age groups were in the clinical trial 2. In total, 90 patients were younger than 65 years (68%), 32 were 65-74 years old (24%), and  10  patients were  75 years and older (8 %).

 

FDA Review

 

Who participated in the trials?

 

The demographic characteristics of populations in Trials 1 and 2 are summarized in Tables 11 and 12.

Table 11. Baseline Demographic Characteristics in Trial 1

 VERZENIO
plus
Fulvestrant
N=446
n (%)
Placebo
plus
Fulvestrant
N=223 n (%)
Total
N=669
n (%)
Sex
Female446 (66.7)223 (33.3)669 (100)
Age
Median (range)59 (32-91)62 (32-87)60 (32-91)
Age <65>291 (65.2)133 (59.6)424 (63.4)
Age 65-74 years114 (25.6)60 (26.9)174 (26.0)
Age ≥75 and <85>38 (8.5)28 (12.6)66 (9.9)
Age ≥85 years3 (0.7)2 (0.9)5 (0.7)
Race
White237 (53.1)136 (61.0)373 (55.8)
Black or African-American9 (2.0)5 (2.2)14 (32.0)
American Indian or Alaska Native18 (4.0)8 (3.6)26 (3.9)
Asian149 (33.4)65 (29.1)214 (32)
Multiple2 (0.5)02 (0.3)
Not reported*31 (7.0)9 (4.0)40 (6.0)
Ethnicity
Hispanic57 (12.9)25 (11.2)82 (12.3)
Non-Hispanic303 (68.4)162 (72.6)465 (69.8)
Not reported*83 (18.7)36 (16.1)119 (17.9)
Geographic Region
US83 (18.6)42 (18.8)125 (18.7)
Canada10 (2.2)4 (1.8)14 (2.1)
Mexico27 (6.1)12 (5.4)39 (5.8)
Europe179 (40.1)100 (44.8)279 (41.7)
Asia147 (33.0)65 (29.1)212 (31.7)

* some countries so not allow the collection of this data

Table 12. Baseline Demographic Characteristics in Trial 2

 VERZENIO 200 mg
N=132
n (%)
Sex
Female132 (100%)
Age
Median (Range)58 (36-89)
Age <65>90 (68.2%)
Age 65-74 years32 (24.2%)
Age ≥75 years10 (7.8%)
Race
White112 (84.8%)
Black or African-American6 (4.5%)
Asian2 (1.5%)
Not reported*12 (9.1%)
Ethnicity
Hispanic0
Non-Hispanic112
Not reported*12
Geographic Region
US70 (53.0%)
Europe (Belgium, Spain, France)62 (47.0%)

* some countries so not allow the collection of this data

Adapted from FDA review

How were the trials designed?

There were two trials that evaluated benefits and side effects of VERZENIO in patients with advanced HR-positive, HER2-negative breast cancer. Each trial was designed differently.

In the first trial, patients had breast cancer that had progressed after treatment with hormone therapy and had not received chemotherapy once the cancer had metastasized. Patients received, at random, either VERZENIO in combination with fulvestrant or placebo in combination with fulvestrant.  The treatment continued until the disease progressed or the side effects became too toxic. Neither the patients nor the health care providers knew which treatment was being given until the trial was completed.
The trial  measured the length of time tumors did not grow after treatment (progression-free survival).

In the second trial patients had breast cancer that had progressed after treatment with hormone therapy and also  have received chemotherapy after the cancer metastasized. All patients received  VERZENIO. The treatment continued until the disease progressed or the side effects became too toxic.
The trial measured the percent of patients whose tumors completely or partially shrank after treatment (objective response rate).
 

How were the trials designed?

The safety and efficacy  efficacy of VERZENIO were evaluated in two clinical trials that enrolled women with hormone receptor (HR)‐positive, human epidermal growth factor negative (HER2 negative) metastatic breast cancer.

Trial 1 was a multicenter, randomized, double blind, placebo controlled trial of VERZENIO + fulvestrant in patients who have had disease progression on previous endocrine therapy. Patients received VERZENIO + fulvestrant or placebo+ fulvestrant twice daily. The primary efficacy outcome measure of the trial was investigator assessed progression free survival.

Trial 2 was a multicenter, single arm, open label trial in patients who have had disease progression after endocrine therapy and have received 1 or 2 prior chemotherapy regimens in the metastatic setting. Patients received VERZENIO twice daily.
The primary objective was investigator assessed ORR (complete response [CR] + partial response [PR]) based on tumor assessments and Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

PRESCRIBING INFORMATION

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Figures 3a and 3b summarizes patients by age in the clinical trials.