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Drug Trial Snapshot: Erleada

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 ERLEADA Package Insert for complete information.

Erleada
(er lee’dah)
Janssen Biotech, Inc.
Approval date: February 14, 2018


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

ERLEADA is a drug for the treatment of prostate cancer that has not spread to other parts of the body (non-metastatic) and no longer responds to a medical or surgical treatment that lowers testosterone (castration-resistant).

How is this drug used?

ERLEADA is a tablet. Four tablets (total of 240 mg) are taken once daily with or without food.

What are the benefits of this drug?

In the trial, ERLEADA increased the patients’ survival during which there was no spreading of the cancer (called metastasis-free survival). The median metastasis-free survival for patients taking ERLEADA was 40.5 months compared to 16.2 months for patients taking a placebo.

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

The primary efficacy outcome measure of the clinical trial was metastasis-free survival (MFS). MFS was defined as the time from randomization to the time of first evidence of blinded independent central review (BICR)-confirmed distant metastasis, defined as new bone or soft tissue lesions or enlarged lymph nodes above the iliac bifurcation, or death due to any cause, whichever occurred first. Additional efficacy endpoints were time to metastasis (TTM), progression-free survival (PFS) time to symptomatic progression, and overall survival (OS).

The efficacy results are shown in Figure 4 and Table 2.

Figure 4. Kaplan-Meier Metastasis-Free Survival (MFS) Curve in ERLEADA Clinical Trial

 Figure summarizes efficacy results for the clinical trial).

ERLEADA Prescribing Information

Table 2: BICR-assessed Efficacy Results in ERLEADA Clinical Trial

EndpointNumber of Events (%)Median [Months (95% CI)]HR (95% CI) p-value (log-rank test)1
ERLEADA+ADT (N=806)Placebo+ADT (N=401)ERLEADA+ADTPlacebo+ADT
Metastasis Free Survival184 (23%)194 (48%)40.51 (NE, NE)16.20 (14.59, 18.40)0.28 (0.23, 0.35) <>
Time to Metastasis175 (22%)191 (48%)40.51 (NE, NE)16.59 (14.59, 18.46)0.27 (0.22, 0.34) <>
Progression-Free Survival200 (25%)204 (51%)40.51 (NE, NE)14.72 (14.49, 18.37)0.29 (0.24, 0.36) <>
ADT: Androgen deprivation therapy

NE=Not Estimable

1All analyses stratified by PSA doubling time, bone-sparing agent use, and locoregional disease status.

ERLEADA Prescribing Information

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

  • Sex: All the patients were men since ERLEADA is for the treatment of prostate cancer.
  • Race: ERLEADA worked similarly in White, Black or African American, and Asian patients.
  • Age: ERLEADA worked similarly in patients below or above 65 years of age, including patients above 75 years of age.

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

The table below shows metastasis-free survival by subgroup. These exploratory analyses should be interpreted with caution.

Table 3. Metastasis Free Survival by Subgroups

 Number of Events/Total N (% of Patients with Event)Median (months)HR (95% CI)1
ERLEADAPlaceboERLEADAPlacebo
Race
White121/524 (23)143/276 (52)40.514.60.26 (0.21, 0.34)
Black11/48 (23)6/20 (30)25.836.80.63 (0.23, 1.72)
Asian14/93 (15)18/47 (38)NE18.50.33 (0.16, 0.67)
Others38/141 (27)27/58 (47)3018.40.40 (0.24, 0.65)
Age
<>19/106 (18)25/43 (58)NE7.30.14 (0.08, 0.27)
65-<>75/307 (24)88/169 (52)NE14.60.25 (0.18, 0.34)
≥7590/393 (23)81/189 (43)40.518.50.42 (0.31, 0.56)
Region
North America70/285 (25)67/134 (50)40.515.70.30 (0.21, 0.42)
Europe93/395 (24)101/204 (50)NE14.80.29 (0.22, 0.39)
Rest of the world21/126 (17)26/63 (41)NE18.50.30 (0.17, 0.54)

HR=hazard ratio; CI=confidence interval; NE=non-estimable

1HR is estimated from an unstratified Cox proportional hazards model

Adapted from FDA review

What are the possible side effects?

ERLEADA may cause serious side effects including falls and bone fractures, and seizures.

The most common side effects of ERLEADA include feeling tired, elevated blood pressure, rash, and diarrhea.

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

The tables below show the side effects and laboratory abnormalities noted in 1201 patients who received at least one dose of study treatment and were included in the safety assessment (safety population).

Table 4. Adverse Reactions Occurring in ≥10% of Patients in ERLEADA Clinical Trial

 ERLEADA N=803Placebo N=398
System/Organ Class Adverse reactionAll Grades %Grade 3-4 %All Grades %Grade 3-4 %
General disorders and administration site conditions
Fatigue1,4391280.3
Musculoskeletal and connective tissue disorders
Arthralgia416080
Skin and subcutaneous tissue disorders
Rash224560.3
Metabolism and nutrition disorders    
Decreased appetite5120.190
Peripheral edema611090
Injury, poisoning and procedural complications
Fall416290.8
Fracture312370.8
Investigations
Weight decreased416160.3
Vascular disorders
Hypertension25142012
Hot flush14090
Gastrointestinal disorders    
Diarrhea201150.5
Nausea180160

1 Includes fatigue and asthenia

2 Includes rash, rash maculo-papular, rash generalized, urticaria, rash pruritic, rash macular, conjunctivitis, erythema multiforme, rash papular, skin exfoliation, genital rash, rash erythematous, stomatitis, drug eruption, mouth ulceration, rash pustular, blister, papule, pemphigoid, skin erosion, and rash vesicular

3 Includes rib fracture, lumbar vertebral fracture, spinal compression fracture, spinal fracture, foot fracture, hip fracture, humerus fracture, thoracic vertebral fracture, upper limb fracture, fractured sacrum, hand fracture, pubis fracture, acetabulum fracture, ankle fracture, compression fracture, costal cartilage fracture, facial bones fracture, lower limb fracture, osteoporotic fracture, wrist fracture, avulsion fracture, fibula fracture, fractured coccyx, pelvic fracture, radius fracture, sternal fracture, stress fracture, traumatic fracture, cervical vertebral fracture, femoral neck fracture, and tibia fracture

4 Grade 4 definitions do not exist for these reactions

5 Includes appetite disorder, decreased appetite, early satiety, and hypophagia

6 Includes peripheral edema, generalized edema, edema, edema genital, penile edema, peripheral swelling, scrotal edema, lymphedema, swelling, and localized edema

ERLEADA Prescribing Information

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

  • Sex: All the patients were men since ERLEADA is for the treatment of prostate cancer.
  • Race: The occurrence of side effects was similar in White, Black or African American or Asian patients.
  • Age: The occurrence of more severe side effects (grade 3-4) in patients treated with ERLADA was higher as age increases.

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

Grade 3-4 adverse reactions occurred in 46% (323/697) of patients 65 years or older and in 51% (197/391) of patients 75 years or older treated with ERLEADA compared to 35% (124/355) of patients 65 years or older and 37% (70/187) of patients 75 years or older treated with placebo.

The table below shows frequent adverse reactions (all grades) by race and age subgroups noted in the clinical trial.

Table 5: Frequent Adverse Reactions by Race and Age Subgroups

 ERLEADA n/N (%)Placebo n/N (%)
Fatigue1
Race
Asian19/92 (21)2/47 (4)
Black/African American11/48 (23)6/20 (30)
White221/522 (42)77/273 (28)
Other/Not Reported62/141 (44)25/58 (43)
Age
<65 years="" of="">42/106 (40)12/43 (28)
65-<75>115/306 (38)46/168 (27)
75 and older156/391 (40)52/187 (28)
Arthralgia
Race
Asian5/92 (5)1/47 (2)
Black/African American10/48 (21)1/20 (5)
White85/522 (16)26/273 (9)
Other/Not Reported29/141 (21)5/58 (9)
Age
<65 years="" of="">16/106 (15)3/43 (7)
65-<75>50/306 (16)13/168 (8)
75 and older63/391 (16)17/187 (9)
Rash2
Race
Asian29/92 (31)1/47 (2)
Black/African American7/48 (15)1/20 (5)
White114/522 (22)17/273 (4)
Other/Not Reported28/141 (20)2/58 (3)
Age
<65 years="" of="">19/106 (18)4/43 (9)
65-<75>55/306 (18)6/168 (6)
75 and older104/391 (27)11/187 (6)
Fall
Race
Asian2/92 (2)3/47 (6)
Black/African American7/48 (15)2/20 (10)
White92/522 (18)26/273 (10)
Other/Not Reported28/141 (20)5/58 (9)
Age
<65 years="" of="">14/106 (13)1/43 (2)
65-<75>38/306 (12)10/168 (6)
75 and older77/391 (20)25/187 (13)
Fracture3
Race
Asian8/92 (9)5/47 (11)
Black/African American2/48 (4)0/20 (0)
White52/522 (10)17/273 (6)
Other/Not Reported20/141 (14)3/58 (5)
Age
<65 years="" of="">9/106 (8)2/43 (5)
65-<75>25/306 (8)5/168 (3)
75 and older48/391 (12)48/187 (26)

1Includes fatigue, asthenia

2Includes rash, rash maculo-papular, rash generalized, urticaria, rash pruritic, rash macular, conjunctivitis, erythema multiforme, rash papular, skin exfoliation, genital rash, rash erythematous, stomatitis, drug eruption, mouth ulceration, rash pustular, blister, papule, pemphigoid, skin erosion, and rash vesicular.

3Includes rib fracture, lumbar vertebral fracture, spinal compression fracture, spinal fracture, foot fracture, hip fracture, humerus fracture, thoracic vertebral fracture, upper limb fracture, fractured sacrum, hand fracture, pubis fracture, acetabulum fracture, ankle fracture, compression fracture, costal cartilage fracture, facial bones fracture, lower limb fracture, osteoporotic fracture, wrist fracture, avulsion fracture, fibula fracture, fractured coccyx, pelvic fracture, radius fracture, sternal fracture, stress fracture, traumatic fracture, cervical vertebral fracture, femoral neck fracture, tibia fracture.

Clinical Trial Data

WHO WAS IN THE STUDIES?

Who participated in the clinical trials?

The FDA approved ERLEADA based on evidence from a clinical trial (NCT01946204) of 1207 patients with prostate cancer that had not spread outside the prostate and that had not responded to castration. The trial was conducted at 332 sites in 26 countries (United States, Canada, several European countries, Israel, Japan, South Korea and Taiwan).

Figures 1, 2, and 3 summarize how many were in the clinical trial by sex, race and age.

Figure 1. Baseline Demographics by Sex

Pie chart summarizing by sex how many patients participates in the clinical trial. In total, 1207 men (100%) participated in the clinical trial).

 FDA review

 Figure 2. Baseline Demographics by Race

Pie chart summarizing the percentage of patients by race in clinical trial. In total, 800 White (66%),140 Asians (12%),  68 Black or African Americans (6%), and 199 Other (16%) patients , participate in the clinical trial.

FDA Review

Table 1. Demographics by Race

 Number of PatientsPercent
Race
White80066
Asian14012
Black or African American686
American Indian or Alaska Native4less than 1
Other2less than 1
Multiple1less than 1
Not Reported*19216

* Data on race and/or ethnicity were not collected in some countries because of local regulations

FDA Review

Figure 3. Baseline Demographics by Age

 Pie charts summarizing how many individuals of certain age groups were in the clinical trial. In total, 149 patients  were younger than 65 years (12%), 476 were 65 to 75 years old (40%) and  582 patients were 75 years and older (48%).

FDA Review

 

Who participated in the Trials?

 

The table below shows the trial demographics.

Table 8. Trial Demographics

 ERLEADA N=806 (%)Placebo N=401 (%)
Sex
Men806 (100)401 (100)
Race
White524 (65)276 (69)
Asian93 (12)47 (12)
Black or African American48 (6)20 (5)
American Indian or Alaska Native4 (0.5)0 (0)
Multiple1 (0.1)0 (0)
Other1 (0.1)1 (0.2)
Not Reported*135 (17)57 (14)
Age (years)
Median (Min, Max)74 (48 - 94)74 (52 - 97)
<>106 (13)43 (11)
65-<>307 (38)169 (42)
≥75393 (48)189 (47)
Ethnicity
Hispanic or Latino11 (1.4)5 (1.2)
Not Hispanic or Latino659 (82)338 (84)
Not Reported*136 (17)58 (14)
Geographic Region
USA224 (28)113 (28)
Rest of the World  
Europe395 (49)204 (51)
Asia83 (10)43 (11)
Canada61 (8)21 (5)
Australia / New Zealand36 (4.5)13 (3.2)
Israel7 (0.9)7 (1.7)

*Data on race and/or ethnicity were not collected in some countries because of local regulations

FDA Review

How were the trials designed?

There was one trial that assessed efficacy and side effects of ERLEADA. Al patients in the trial had a prostate cancer that had not spread outside the prostate and that had not responded to castration. Patients were randomly assigned to receive ERLEADA or placebo. Neither the patient nor the healthcare provider knew which treatment was being given until after the trial was completed. All patients also received either hormone therapy or surgery to lower the amount of testosterone in their body.

 

The efficacy of ERLEADA was assessed by measuring the length of time that tumor did not spread to other parts of the body or that death occurred after starting treatment. That is called metastasis-free survival (MFS).

How were the trials designed?

Patients with non-metastatic castration resistant prostate cancer (NM-CRPC) were randomized 2:1 to receive either ERLEADA orally at a dose of 240 mg once daily or placebo in a multicenter, double-blind, clinical trial (NCT01946204). All patients received concomitant gonadotropin-releasing hormone (GnRH) analog or had a bilateral orchiectomy. The primary efficacy outcome was metastasis-free survival (MFS), defined as the time from randomization to the time of first evidence of blinded independent central review (BICR)-confirmed distant metastasis, defined as new bone or soft tissue lesions or enlarged lymph nodes above the iliac bifurcation, or death due to any cause, whichever occurred first. Additional efficacy endpoints were time to metastasis (TTM), progression-free survival (PFS) time to symptomatic progression, and overall survival (OS).

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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