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ERLEADA® (apalutamide)

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ERLEADA - LIBERTAS Study

Last Updated: 03/03/2026

SUMMARY  

  • LIBERTAS (NCT05884398) is an ongoing, phase 3, prospective, randomized, open-label, multicenter, global study evaluating the efficacy and safety of ERLEADA with intermittent vs continuous androgen deprivation therapy (ADT) following undetectable prostate-specific antigen (PSA) response (<0.2 ng/mL) in patients with newly diagnosed metastatic castration-sensitive prostate cancer (mCSPC), inclusive of all gender identities. After 6 months of initial treatment with ERLEADA and continuous ADT, patients with PSA response enter the main treatment phase and will be treated with either ERLEADA and intermittent ADT or ERLEADA and continuous ADT. The dual primary endpoints are radiographic progression-free survival and hot flash severity score and frequency at 18 months from randomization.1-3 During the initial treatment phase:
  • A patient subgroup analysis was conducted in Chinese patients who completed the initial 6-month treatment phase (n=36). All patients achieved ≥50% reduction in PSA (PSA50), 97.2% achieved ≥90% reduction in PSA (PSA90), and 61.1% reached ≥0.2 ng/mL PSA (PSA0.2) by 6 months and no new safety signals were observed.8

CLINICAL DATA

LIBERTAS Study

LIBERTAS is an ongoing phase 3 study evaluating the efficacy and safety of ERLEADA with intermittent vs continuous ADT following PSA response in patients with newly diagnosed mCSPC, inclusive of all gender identities.1-3

Study Design/Methods

LIBERTAS Study Design1-3,7

Abbreviations: 99mTc, technetium-99m; ADT, androgen deprivation therapy; APA, apalutamide; CT, computed tomography; ECOG, Eastern Cooperative Oncology Group; GAC, gender-affirming care; LAPC, locally advanced prostate cancer; LPC, localized prostate cancer; mCRPC, metastatic castration-resistant prostate cancer; mCSPC, metastatic castration-sensitive prostate cancer; MRI, magnetic resonance imaging; NGI, next-generation imaging; OS, overall survival; PC, prostate cancer; PFS2, second progression-free survival; PS, performance status; PO, orally; PRO, patient-reported outcome; PSA, prostate-specific antigen; QD, once daily; QoL, quality of life; R, randomization; rPFS, radiographic progression-free survival; SOC, standard of care.
aPatient enrollment includes a degendered and transgender-inclusive protocol, as well as nonbinary and gender-diverse patients.
b≤3 months of ADT prior to enrollment (except patients receiving ADT as part of their GAC).
cPatients with ECOG PS 2-3 are eligible if the score is related to stable physical limitations (eg. spinal cord injury, blindness) and not related to PC or associated therapy.
dSevere or unstable angina, myocardial infarction, symptomatic congestive heart failure, uncontrolled hypertension, clinically significant arterial or venous thromboembolic events.
ePatients undergoing GAC or with a variation in physical development who receive exogenous hormones will be evaluated as a separate cohort with regard to their outcomes in a more descriptive manner. These patients will not be randomized for the main treatment phase and will be continuously treated with ERLEADA from study initiation until disease progression.
fChoice of ADT (gonadotropin-releasing hormone agonist or antagonist) at discretion of investigator.
g272 patients were randomized including 1 patient without assignment of randomized treatment (intent-to-treat population n=271).

hPatients in Arm A can restart ADT with new or worsening cancer symptoms, PSA increase to >10 ng/mL (or return to baseline level when PSA was <10 ng/mL before starting ADT) or PSA doubling time <6 months.
iPatients with a PSA level <0.2 ng/mL after 6 months of treatment with ERLEADA and ADT during the initial treatment phase, will enter the main treatment phase.
jConventional imaging (CT/MRI and 99mTc bone scans) will be used for the assessment of radiographic progression.
kQoL assessments will be based on subjective PROs and objective data from digital health tools. Hot flashes will be evaluated using the Hot Flash Related Daily Interference Scale PRO questionnaire/hot flash diary data.
lFindings from digital health tools measure sleep, activity and neurocognitive function, and PROs, including physical and mental wellbeing.

Results

Patient Characteristics
  • The planned enrollment goal (~333 patients)1,2 was met, with a total of 420 patients across 73 sites in 9 countries enrolled in the initial treatment phase.4,5
  • There were 272 patients with undetectable PSA (<0.2 ng/mL) randomized to the main treatment phase.4,5
  • Select baseline patient characteristics are shown in Table: Select Baseline Patient Characteristics.4,5
  • Patients who had prostate-specific membrane antigen positron emission tomography (PSMA-PET) at screening had a lower disease burden (eg, baseline PSA and disease volume) vs the overall population.5

Select Baseline Patient Characteristics4,5,7
Characteristic
Full Analysis
(N=420)
With Hot Flash at Baseline
(n=250)
Without Hot Flash at Baseline
(n=170)
Median age, years (IQR)
70 (64-75)
69 (63-75)
72 (67-76)
   ≥75 years old, n (%)
124 (30)
67 (27)
57 (34)
Gender identity, n (%)
   Men
235 (56.0)
-
-
   Not reported or declined to answer
185 (44.0)
-
-
Median time from diagnosis to randomization, months (range)
10.25 (6.1-271.1)
-
-
Median (IQR) time from mCSPC diagnosis to initial treatment, months
2.3 (1.4-3.5)
2.5 (1.5-3.5)
2.1 (1.4-3.2)
Race, n (%)
   White
297 (71)
179 (72)
118 (69)
   Asian
39 (9)
22 (9)
17 (10)
   Black or African American
36 (9)
21 (8)
15 (9)
   Othera
48 (11)
28 (11)
20 (12)
ECOG PS, n (%)
   0
312 (74)
183 (73)
129 (76)
   1
105 (25)
65 (26)
40 (24)
   2
3 (0.7)
2 (1)
1 (1)
Gleason score at diagnosis, n (%)b
   ≤7
139 (33)
83 (33)
56 (33)
   >7
269 (64)
160 (64)
109 (64)
Metastasis stage at diagnosis, n (%)
   M0 or MX
146 (35)
79 (32)
67 (39)
   M1
273 (65)
171 (68)
102 (60)
   Missing
1 (0.2)
-
1 (0.6)
Visceral metastases at baseline, n (%)
68 (16)
45 (18)
25 (15)
   Liver metastases
8 (1.9)
Bone metastases at baseline, n (%)
344 (82)
218 (87)
127 (75)
High volume,c n(%)
202 (48)
125 (50)
79 (46)
Received prior ADT for mCSPC, %
65
73
54
Median baseline PSA, ng/mL (range)
7.32 (0.0-4433.0)
-
-
Patients with hot flash at baseline, %
60
-
-
Abbreviations: ADT, androgen deprivation therapy; ECOG PS, Eastern Cooperative Oncology Group performance status; IQR, interquartile range; mCSPC, metastatic castration-sensitive prostate cancer; PSA, prostate-specific antigen.
aIncludes patients of other, multiple, not reported/unknown, American Indian or Alaska Native race.bMissing data: full analysis (n=12), “with hot flash at baseline” (n=7), “without hot flash at baseline” (n=5).
cDefined as either visceral metastases or ≥4 bone lesions, including ≥1 outside of the vertebral column or pelvis based on the CHAARTED criteria. Missing data: full analysis (n=3), “without hot flash at baseline” (n=3).
Initial Treatment Results

Note: All analyses are based on the August 11, 2025, data cut; data clean-up was not 100% completed at the time of the data cut.

Hot Flash

Hot Flash Incidence and Severity5
Full Analysis (N=420)
With Hot Flash at Baseline
(n=248)
Without Hot Flash at Baseline (n=172)
Hot flash incidence, n/N (%)
   At baseline
248/404 (61)
248/248 (100)
0/156 (0)
   At 6 months
295/344 (86)
184/206 (89)
111/138 (80)
Median (IQR) severity-adjusted hot flash scorea
   At baseline
0.6 (0.0-3.7)
2.5 (0.8-7.6)
NA
   At 6 months
5.2 (1.3-11.4)
6.2 (2.0-12.5)
3.7 (0.9-10.0)
Deterioration in hot flash during the initial treatment phase, n/N (%)b
   Increase of ≥2 hot flashes per day
   from baseline on average
194/314 (62)
117/199 (59)
77/115 (67)
≥50% increase in severity-adjusted
   hot flash score from baselinec
NA
135/199 (68)
NA
Abbreviations: IQR, interquartile range; NA, not applicable.
aTotal severity score: each hot flash event multiplied by severity factor (1-mild, 2-moderate, 3-severe, 4-very severe) and summed across collection days. Average daily: total severity score divided by number of collection days.
bPatients were included if hot flash data were available from all 3 visits (baseline, cycle 4 day 1, and cycle 7 day 1).
cCalculated only for patients with hot flash at baseline.

Overall Hot Flash Burden Determined by Severity-Adjusted Hot Flash Score (Combining Frequency and Severity) During the Initial Treatment Phase5,6
Hot Flash Incidence,
n/N (%)
Median (IQR) Severity-Adjusted Hot Flash Scorea
Baseline
3 Months
6 Months
Baseline
3 Months
6 Months
Full analysis
(N=420)
248/404
(61)
340/384
(89)
295/344
(86)
0.6
(0-3.7)
5.0
(1.7-11.9)
5.2
(1.3-11.4)
PSA responders
(n=271)
161/261
(62)
227/258
(88)
223/262
(85)
0.6
(0-3.1)
4.6
(1.5-11.7)
4.5
(1.1-11.3)
PSA nonrespondersb (n=149)
87/143
(61)
113/126
(90)
72/82
(88)
0.5
(0-4.9)
5.8
(2.0-12.7)
7.1
(2.4-11.9)
With prestudy ADTc (n=274)
181/263
(69)
221/250
(88)
190/227 (84)
1.1
(0-6.3)
4.9
(1.6-11.2)
4.9
(1.1-10.4)
Without prestudy ADTc (n=146)
67/141
(48)
119/134
(89)
105/117 (90)
0
(0-1.1)
5.5
(1.8-14.9)
5.8
(1.5-12.7)
Abbreviations: ADT, androgen deprivation therapy; IQR, interquartile range; mCSPC, metastatic castration-sensitive prostate cancer; PSA, prostate-specific antigen.
aTotal severity score: each hot flash event multiplied by severity factor (1-mild, 2-moderate, 3-severe, 4-very severe) and summed across collection days. Average daily: total severity score divided by the number of collection days.
bNonresponders are patients with PSA ≥0.2 ng/mL response at 6 months.
cPrior ADT for mCSPC.

Peak Hot Flash Severity from Baseline to 6 Months5,6
Full Analysis Set
With Prestudy ADT for mCSPC
Without Prestudy ADT for mCSPC
Baseline (n=404)
3 Months
(n=384)
6 Months (n=344)
Baseline (n=263)
3 Months (n=250)
6 Months (n=227)
Baseline (n=141)
3 Months (n=134)
6 Months (n=117)
No hot flash, %
39
11
14
31
12
16
52
11
10
Mild, %
21
23
21
24
25
22
16
18
19
Moderate, %
22
34
36
24
33
33
18
36
42
Severe, %
6
14
12
7
12
14
5
17
9
Very severe, %
12
18
17
14
18
15
9
18
21
Abbreviations: ADT, androgen deprivation therapy; mCSPC, metastatic castration-sensitive prostate cancer.
Hot flash severity was captured by the patients based on guidance provided. The severity grades were based on duration of hot flash, physical symptoms, emotional symptoms, and action taken. Highest severity is the most severe hot flash recorded at any time point associated with that analysis visit.
Prestudy ADT, Serum Testosterone, and PSA Levels

PSA Decline After 3 and 6 Months of Initial Treatment4
PSA Levels
Treated Patients
PSA decline after 3 months of treatment, n (%)
N=420
   ≥50%a
381 (90.7)
   ≥90%a
259 (61.7)
   <0.2 ng/mL
174 (41.4)
Median time to confirmed PSA decline after 3 months, months (range)
   ≥50%a
1.9 (1.0-5.3)
   ≥90%a
1.9 (1.1-5.6)
   <0.2 ng/mL
2.8 (1.5-5.7)
PSA decline after 6 months of treatment, n (%)
n=143
   ≥50%a
137 (95.8)
   ≥90%a
113 (79.0)
   <0.2 ng/mL
101 (70.6)
Abbreviation: PSA, prostate-specific antigen.
aDecline from baseline.

Prestudy ADT, Testosterone, and PSA Levels5
Full Analysis (N=420)
With Hot Flash at Baseline
(n=248)
Without Hot Flash at Baseline (n=172)
Prestudy ADT
   Prestudy ADT for mCSPC, n (%)
274 (65)
181 (73)
93 (54)
   Median (IQR) time from ADT initiation
   to initial treatment, monthsa
1.6 (1.0-2.6)
1.7 (1.2-2.6)
1.4 (0.8-2.2)
Testosterone
   Median (IQR) serum testosterone at
   baseline, nmol/Lb
0.8 (0.4-11.2)
0.6 (0.4-6.2)
5.2 (0.5-13.4)
   Median (IQR) serum testosterone at
   6 months, nmol/Lb
0.5 (0.4-0.8)
0.5 (0.4-0.8)
0.5 (0.4-0.8)
PSA
   Median (IQR) PSA at baseline, ng/mL
7.3 (1.7-43.7)
4.9 (1.1-36.6)
11.8 (3.2-61.6)
   Confirmed PSA <0.2 ng/mL during the
   initial treatment phase, n (%)c
294 (70)
174 (70)
120 (70)
   Median (IQR) time to confirmed PSA
   <0.2 ng/mL, months
2.8 (1.9-3.7)
2.8 (1.9-3.7)
2.8 (1.9-3.7)
   Confirmed PSA <0.02 ng/mL during
   the initial treatment phase, n (%)c
88 (21)
55 (22)
33 (19)
   Median (IQR) time to confirmed PSA
   <0.02 ng/mL, months
4.6 (3.7-5.1)
4.6 (3.7-5.1)
4.6 (3.7-5.1)
Abbreviations: ADT, androgen deprivation therapy; IQR, interquartile range; mCSPC, metastatic castration-sensitive prostate cancer; PSA, prostate-specific antigen.
aIncludes only dosing periods with non-missing start and end dates.
bBaseline n=413 and 6 months n=246 in the full analysis set; baseline n=242 and 6 months n=147 in “with hot flash at baseline”; and baseline n=171 and 6 months n=99 in “without hot flash at baseline”. cBest response during the initial treatment phase.
Impact of Baseline Hot Flashes on Sleep Metrics
  • The impact of baseline hot flashes on sleep metrics was evaluated using triaxial acceleration data from the Ametris CentrePoint® Insight Watch, which the patients wore on their wrist throughout the study.7
    • Actigraphy adherence ranged between 90.5%-92.6% across baseline, cycle 4 day 1, and cycle 7 day 1 timepoints in the full analysis, with similar adherence across patients with and without hot flash at baseline.
    • After starting the initial treatment phase, patients with hot flashes at baseline experienced a significantly greater increase in wake after sleep onset (WASO) and number of awakenings, and a significantly greater decline in sleep efficiency compared with those without hot flashes at baseline (P<0.05). By the end of the initial treatment phase, patients with hot flashes at baseline maintained a significantly higher WASO and lower sleep efficiency compared with those without hot flashes at baseline (P<0.05). See Table: Digital Sleep Metrics.
    • Patient Health Questionnaire-9 (PHQ-9) scores indicated higher sleep disturbances and fatigue over the initial treatment phase for all enrolled patients, consistent with the digital sleep metric data.
    • During the initial treatment phase, depression severity scores and Patient Global Impression of Change (PGIC) scores were stable.

Digital Sleep Metricsa,7
Parameter
Baseline
Cycle 4 Day 1
Cycle 7 Day 1
With Hot Flash at Baseline
Without Hot Flash at Baseline
Pb Value
With
Hot Flash at Baseline
Without Hot Flash at Baseline
Pb Value
With Hot Flash at Baseline
Without Hot Flash at Baseline
Pb Value
All enrolled patients
n=227
n=143
n=214
n=129
n=176
n=105
Median (IQR) WASO,c minutes
72.71
(56.86-93.79)
70.08
(43.93-95.41)
0.135
79.80
(61.52-100.19)
73.75
(55.30-91.73)
0.028
73.45
(57.75-94.38)
65.43
(49.57-89.17)
0.042
Median (IQR) number of awakenings
17.50
(13.71-22.17)
16.40
(12.00-21.90)
0.114
19.00
(14.81-23.62)
17.29
(12.69-21.73)
0.019
18.37
(13.72-22.71)
16.25
(12.12-20.83)
0.114
Median (IQR) sleep efficiency
0.85
(0.80-0.88)
0.86
(0.80-0.90)
0.080
0.84
(0.80-0.87)
0.85
(0.82-0.89)
0.012
0.85
(0.81-0.88)
0.87
(0.84-0.89)
0.025
ADT-naïve patients
n=59
n=65
n=57
n=60
n=44
n=51
Median (IQR) WASO,c minutes
76.57
(58.59-94.78)
70.08
(39.00-92.40)
0.065
81.93
(69.92-111.50)
72.57
(54.97-90.81)
0.006
87.72
(69.44-110.72)
65.88 (49.58-87.31)
0.001
Median (IQR) number of awakenings
18.50
(14.91-22.94)
17.62
(10.64-21.91)
0.092
21.21 (17.50-25.25)
17.35
(12.66-22.28)
0.011
21.54 (17.53-25.03)
15.83 (13.10-22.46)
0.009
Median (IQR) sleep efficiency
0.84
(0.80-0.87)
0.86
(0.82-0.92)
0.011
0.82
(0.78-0.86)
0.85
(0.82-0.89)
0.001
0.82
(0.81-0.86)
0.87 (0.84-0.89)
0
Abbreviations: ADT, androgen deprivation therapy; IQR, interquartile range; WASO, wake after sleep onset.aDerived from triaxial acceleration data collected via the device.bWilcoxon P value.cSleep/wake classification was performed using the Cole-Kripke or Sadeh algorithm.
Safety
  • Hot flash was reported as a TEAE that occurred in 41% of patients in the full analysis set, of which 84% were grade 1.5

Literature Search

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 09 February 2026.

References

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1 Azad A, Badillo MA, Dong Q, et al. Apalutamide plus intermittent versus continuous androgen deprivation therapy in participants with metastatic hormone-sensitive prostate cancer: LIBERTAS phase 3 study design. Poster presented at: 2024 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium; January 25-27, 2024; San Francisco, CA.  
2 Azad A, Musto C, Netanel S, et al. LIBERTAS, a degendered and transgender-inclusive phase 3 study of apalutamide plus intermittent versus continuous androgen deprivation therapy in participants with metastatic hormone-sensitive prostate cancer. Poster presented at: 2024 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2024; Chicago, IL.  
3 Janssen Research & Development, LLC. A study of an intermittent ADT approach with apalutamide monotherapy in participants with mCSPC (LIBERTAS). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2020- [cited 2026 February 09]. Available from: https://clinicaltrials.gov/study/NCT05884398 NLM Identifier: NCT05884398.  
4 Azad A, Badillo MA, Dong Q, et al. Deep prostate-specific antigen decline among early participants in LIBERTAS, a phase 3 study of apalutamide plus continuous versus intermittent androgen deprivation therapy in metastatic castration-sensitive prostate cancer. Poster presented at: 2025 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium; February 13-15, 2025; San Francisco, CA.  
5 Morgans AK, Azad AA, Santoyo MAB, et al. Prevalence and severity of hot flashes and their association with prostate-specific antigen response: results from the initial treatment phase of LIBERTAS, a phase 3 study in metastatic hormone-sensitive prostate cancer. Poster presented at: 2025 European Society for Medical Oncology (ESMO) Congress; October 17-21, 2025; Berlin, Germany.  
6 Morgans AK, Azad AA, Santoyo MAB, et al. Supplement to: Prevalence and severity of hot flashes and their association with prostate-specific antigen response: results from the initial treatment phase of LIBERTAS, a phase 3 study in metastatic hormone-sensitive prostate cancer. Poster presented at: 2025 European Society for Medical Oncology (ESMO) Congress; October 17-21, 2025; Berlin, Germany.  
7 Azad A, Santoyo MAB, Morgans AK, et al. Impact of baseline hot flashes on sleep metrics during initial treatment in LIBERTAS clinical trial. Poster presented at: 2026 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium; February 26-28, 2026; San Francisco, CA.  
8 Dong Q, Li L, Li Z, et al. Deep PSA decline in the Chinese subgroup of LIBERTAS, a phase 3 study of apalutamide plus continuous versus intermittent androgen deprivation therapy in metastatic castration-sensitive prostate cancer. Poster presented at: 2026 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium; February 26-28, 2026; San Francisco, CA.