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

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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 Fulvestrant	Placebo plus Fulvestrant
Progression-Free Survival	N=446	N=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-value	0.553 (0.449, 0.681)
p-value	p<>
Objective Response for Patients with Measurable Disease	N=318	N=164
Objective response ratea (n, %), 95% CI	153 (48.1)	35 (21.3)
95% CI	42.6, 53.6	15.1, 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 Assessed	Independent Review
Objective Response Ratea, n (%)	26 (19.7)	23 (17.4)
95% CI (%)	13.3, 27.5	11.4, 25.0
Median Time to Response	3.7 months	4.0 months
Range	1.1-14.2 months	1.7-9.9 months
Median Duration of Response	8.6 months	7.2 months
95% CI (%)	5.8, 10.2	5.6, 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

	N	HR	95% CI
Age
< 65 Years old	424	0.52	0.40, 0.67
>= 65 Years old	245	0.63	0.45, 0.87
Race
White	373	0.63	0.48, 0.82
Asian	214	0.51	0.35, 0.73
Other	82	0.43	0.21, 0.85
Region
USA	121	0.68	0.42, 1.09
Rest of World	548	0.53	0.42, 0.66

HR=hazard ratio; CI=confidence interval

FDA Review

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

	N	ORR	95% CI
Age
< 65 Years old	90	23.3%	15.0, 33.4
>= 65 Years old	42	11.9%	4.0, 25.6
Race
White	112	19.6%	12.7, 28.2
Other	8	25%	3.2, 65.1
Region
USA	70	21.4%	12.5, 32.8
Rest of World	62	17.7%	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 1^a

	VERZENIO plus Fulvestrant N=441			Placebo plus Fulvestrant N=223
Adverse Reactions (MedDRA) System Organ Class	All Grades %	Grade 3 %	Grade 4 %	All Grades %	Grade 3 %	Grade 4 %
Gastrointestinal Disorders
Diarrhea	86.4	13.4	0	24.7	0.4	0
Nausea	45.1	2.7	0	22.9	0.9	0
Vomiting	25.9	0.9	0	10.3	1.8	0
General Disorders and Administration Site Conditions
Fatigueb	39.9	2.7	0	26.9	0.4	0
Blood and Lymphatic System Disorders
Neutropeniac	46.0	23.6	2.9	4.0	1.3	0.4
Anemiad	29.0	7.0	0.2	3.6	0.9	0
Leukopeniae	28.3	8.6	0.2	1.8	0	0
Thrombocytopeniaf	15.6	2.0	1.4	2.7	0	0.4
Investigations
Alanine aminotransferase increased	13.4	3.9	0.2	5.4	1.8	0
Aspartate aminotransferase increased	12.2	2.3	0	6.7	2.7	0
Skin and Subcutaneous Tissue Disorders
Alopecia	15.6	0	0	1.8	0	0

^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 Class	All Grades %	Grade 1 %	Grade 2 %	Grade 3 %	Grade 4 %
Gastrointestinal Disorders
Diarrhea	90.2	41.7	28.8	19.7	0
Nausea	64.4	39.4	20.5	4.5	0
Vomiting	34.8	22.7	10.6	1.5	0
Dry mouth	13.6	12.1	1.5	0	0
Stomatitis	13.6	11.4	2.3	0	0
General Disorders and Administration Site Conditions
Fatiguea	65.2	21.2	31.1	12.9	0
Blood and Lymphatic System Disorders
Neutropeniab	37.1	1.5	11.4	18.9	5.3
Anemiac	25.0	8.3	12.1	4.5	0
Thrombocytopeniad	20.5	9.8	6.8	3.8	0
Leukopeniae	17.4	2.3	9.1	5.3	0.8
Metabolism and Nutrition Disorders
Decreased appetite	45.5	28.0	14.4	3.0	0
Nervous System Disorders
Dysgeusia	12.1	10.6	1.5	0	0
Skin and Subcutaneous Tissue Disorders
Alopecia	12.1	9.8	2.3	0	0

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 Reaction	VERZENIO plus fulvestrant, N=287	Placebo plus fulvestrant, N=133	VERZENIO plus fulvestrant, N=154	Placebo plus fulvestrant, N=90
Diarrhea	249 (86.8)	27 (20.3)	132 (85.7)	28 (31.1)
Nausea	117 (40.8)	29 (21.8)	82 (53.2)	22 (24.4)

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

	White		Asian
Adverse Reaction	VERZENIO plus fulvestrant, N=234	Placebo plus fulvestrant, N=136	VERZENIO plus fulvestrant, N=148	Placebo plus fulvestrant, N=65
Diarrhea	200 (85.5)	38 (27.9)	134 (90.5)	13 (20.0)
Nausea	121 (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
Diarrhea	82 (91.1)	37 (88.1)
Nausea	57 (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

Figure 1b. Baseline Demographics by Sex-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

Figure 2b. Baseline Demographics by Race-Trial 2

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

Race	Trial 1		Trial 2
	Number of Patients	Percentage	Number of Patients	Percentage
White	373	56	112	85
Asian	214	32	2	1
Black or African American	14	2	6	5
American Indian or Alaska Native	26	4	0	0
Multiple	2	less than 1	0	0
Missing*	40	6	12	9

FDA Review

 

 

 

Figure 3a. Baseline Demographics by Age-Trial 1

Figure 3b. Baseline Demographics by Age-Trial 2

 

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
Female	446 (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 years	114 (25.6)	60 (26.9)	174 (26.0)
Age ≥75 and <85>	38 (8.5)	28 (12.6)	66 (9.9)
Age ≥85 years	3 (0.7)	2 (0.9)	5 (0.7)
Race
White	237 (53.1)	136 (61.0)	373 (55.8)
Black or African-American	9 (2.0)	5 (2.2)	14 (32.0)
American Indian or Alaska Native	18 (4.0)	8 (3.6)	26 (3.9)
Asian	149 (33.4)	65 (29.1)	214 (32)
Multiple	2 (0.5)	0	2 (0.3)
Not reported*	31 (7.0)	9 (4.0)	40 (6.0)
Ethnicity
Hispanic	57 (12.9)	25 (11.2)	82 (12.3)
Non-Hispanic	303 (68.4)	162 (72.6)	465 (69.8)
Not reported*	83 (18.7)	36 (16.1)	119 (17.9)
Geographic Region
US	83 (18.6)	42 (18.8)	125 (18.7)
Canada	10 (2.2)	4 (1.8)	14 (2.1)
Mexico	27 (6.1)	12 (5.4)	39 (5.8)
Europe	179 (40.1)	100 (44.8)	279 (41.7)
Asia	147 (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
Female	132 (100%)
Age
Median (Range)	58 (36-89)
Age <65>	90 (68.2%)
Age 65-74 years	32 (24.2%)
Age ≥75 years	10 (7.8%)
Race
White	112 (84.8%)
Black or African-American	6 (4.5%)
Asian	2 (1.5%)
Not reported*	12 (9.1%)
Ethnicity
Hispanic	0
Non-Hispanic	112
Not reported*	12
Geographic Region
US	70 (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.