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ERLEADA®

(apalutamide)

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ERLEADA® (apalutamide)

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ERLEADA® (apalutamide) - TITAN study

Last updated: 04/28/2025

Overview1

TITAN (NCT02489318) was a phase 3, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the efficacy and safety of ERLEADA compared with placebo in patients with mCSPC

N=1052

An overview of the TITAN study design and results is available in video format
LINK.

Key eligibility criteria1

  • mCSPC
  • Metastatic disease documented by ≥1 lesion on bone scan
  • With or without visceral or lymph node metastasis
  • ECOG PS 0 or 1
  • Prior therapy limitations:
    • Docetaxela
    • ADT for ≤6 months for mCSPC or ≤3 years total for localized prostate cancer
    • 1 course of radiation or surgical therapy for symptoms of metastatic disease
    • Other localized treatments such as radiation therapy and prostatectomy completed ≤1 year ago

aMaximum 6 cycles, no evidence of progression during treatment or before randomization.

Study design1,2

aAll patients received ADT via a GnRH analog or surgical castration.
bBased on results from this first planned interim analysis, the IDMC recommended unblinding to allow crossover of patients (without progression) receiving placebo to receive apalutamide.

Efficacy results1,3

  • The dual primary endpoints for the primary and final analyses are described below.
Endpoints ERLEADA
(n=525) 		Placebo
(n=527)
Primary Analysis
Median rPFS, months NE 22.1
HR (95% CI); P-value 0.48 (0.39-0.60); <0.001
Median OS, months NE NE
HR (95% CI); P-value 0.67 (0.51-0.89); 0.005
Final Analysisa
Median OS, months NR 52.2
HR (95% CI); P-value 0.65 (0.53-0.79); <0.0001

aThe final analysis provided mature OS results without formal statistical inference.

Safety results3,4

  • All-grade TEAEs reported during the final analysis are described below.
AEs, n (%) ERLEADA
(n=524) 		Placebo
(n=527)
≥1 TEAEa 510 (97.3) 510 (96.8)
Serious TEAEa 153 (29.2) 115 (21.8)
Leading to treatment discontinuation 62 (11.8) 30 (5.7)
Leading to death 20 (3.8) 17 (3.2)
Treatment-related TEAEs (≥5% of patients)
≥1 treatment-related TEAE 319 (60.9) 221 (41.9)
Rash 92 (17.6) 12 (2.3)
Pruritus 43 (8.2) 13 (2.5)
Fatigue 71 (13.5) 46 (8.7)
Hot flush 67 (12.8) 52 (9.9)
Hypertension 28 (5.3) 21 (4.0)

aGrade 5 events were excluded.

Additional analyses5-36

  • Additional analyses evaluated efficacy, safety, and HRQoL in patients based on age, disease volume, number of metastases, timing of metastasis presentation, D0 or D1 at diagnosis, prior docetaxel treatment, exposure, PSA kinetics and relationship to rPFS, OS and HRQoL, progression status, high- and low-risk mCSPC, PFS2 by first subsequent therapy (specifically hormonal vs taxane therapy) after discontinuing study treatment, use with or without concomitant OACs, and baseline comorbidities (CV or metabolic risk factors).
  • Additional analyses evaluating molecular signatures, subtypes, and androgen receptor activity and aberrations with long term outcomes have been reported.
  • Patient subgroup analyses were conducted in Latin American, Japanese, and East Asian patients.

Note: ADT, androgen deprivation therapy; AE, adverse event; CI, confidence interval; CV, cardiovascular; D0, progression to mCSPC after localized disease; D1, de novo mCSPC; ECOG PS, Eastern Cooperative Oncology Group Performance Status; GnRH, gonadotropin- releasing hormone; HR, hazard ratio; IDMC, independent data-monitoring committee; mCSPC, metastatic castration-sensitive prostate cancer; NE, not estimable; NR, not reached; OAC, oral anticoagulant; OS, overall survival; PFS2, second progression-free survival; PO, orally; PSA, prostate-specific antigen; rPFS, radiographic progression-free survival; TEAE, treatment-emergent adverse event.

  • TITAN (NCT02489318) was a phase 3, randomized, double-blind, placebo-controlled, multicenter study conducted at 260 sites in 23 countries within North America, Central America, South America, Europe, and Asia-Pacific that evaluated the efficacy and safety of ERLEADA plus ADT compared with placebo plus ADT in patients with mCSPC (N=1052).1-3,37
  • All patients were required to have a documented diagnosis of adenocarcinoma of the prostate, distant metastatic disease (≥1 lesion on bone scan, with or without visceral or lymph node involvement), and castration-sensitive disease (ie, patients who are not receiving ADT at the time of progression).1

aPatients who had received a GnRH agonist ≤28 days before randomization were required to take a first-generation antiandrogen for ≥14 days before randomization, and the antiandrogen must have been discontinued before randomization. Patients were assessed for eligibility (≤6 weeks before randomization) and efficacy (during treatment cycles 3 and 5 and every fourth cycle thereafter) per modified RECIST version 1.1 using CT or MRI of the chest, abdomen, and pelvis and per PCWG2 criteria via bone scan.
bMaximum 6 cycles, no evidence of progression during treatment or before randomization.
cSuch as radiation therapy and prostatectomy.
dAll patients received ADT via a GnRH analog or surgical castration.
eIn the final analysis, OS results did not include formal statistical inference and the updated analyses presented for secondary endpoints were based on the final data cutoff and performed without formal statistical retesting. The final formal statistical testing for all secondary endpoints was performed at the time of the first interim analysis.

Dual primary endpoints1

  • rPFSa
  • OS

Secondary endpoints1,37

  • Time to initiation of cytotoxic chemotherapy
  • Time to pain progression, assessed by BPI-SF item 3 (worst pain)
  • Time to skeletal-related eventb
  • Time to chronic opioid use

Exploratory endpoints1,28,39

  • Time to PSA progressionc
  • PFS2d
  • Time to symptomatic local progression
  • PROs, assessed by the FACT-P questionnaire, EuroQoL EQ-5D-5L questionnaire, BFI, and BPI-SF

Ad hoc endpoint4

  • Time to castration resistancee

Secondary objective1

  • A prespecified analysis of treatment outcomes for patients with low- or high-volumef mCSPC was evaluated.

aDefined as time from randomization to first imaging-based documentation of disease progression (progression of soft issue lesions measured by CT or MRI or new bone lesions on bone scan) or death, whichever occurred first.
bDefined as time from randomization to first observation of a skeletal-related event (symptomatic pathologic fracture, spinal cord compression, radiation to bone, or surgery to bone).
cDefined as time from randomization to PSA progression per PCWG2 criteria.
dDefined as time from randomization to first occurrence of investigator-assessed disease progression (PSA progression, progression on imaging, or clinical progression) while the patient was receiving first subsequent treatment for prostate cancer or death from any cause, whichever occurred first.
eDefined as time from randomization to radiographic disease progression, PSA progression per PCWG2, or symptomatic skeletal event, whichever occurred first.
fLow-volume mCSPC was defined as the presence of bone lesions not meeting the high-volume disease definition, and high-volume mCSPC was defined as visceral metastases and ≥1 bone lesion or ≥4 bone lesions with ≥1 outside the axial skeleton.

  • Patient demographic and disease characteristics were well balanced between the 2 groups, and there were no substantial differences.1
  • Most patients were found to have metastatic disease at initial prostate cancer diagnosis (ERLEADA group, 78.3%; placebo group, 83.7%), and 62.7% of patients met the criteria for high-volume mCSPC compared with 37.3% with low-volume mCSPC.1
  • Over 70% of patients in both groups described having no pain (score 0) or mild pain (score 1-3) at baseline based on mean BPI-SF pain score results; the median baseline FACT-P total score was 113 for both groups (scores range from 0 to 156; higher scores indicate more favorable HRQoL).1,32

Select baseline patient and disease characteristics1,37

ERLEADA Group
(n=525) 		Placebo Group
(n=527)
Median age, years (range) 69 (45-94) 68 (43-90)
Race, n (%)
White 354 (67.4) 365 (69.3)
Asian 119 (22.7) 110 (20.9)
Black or African American 10 (1.9) 9 (1.7)
American Indian or Alaska Native 6 (1.1) 13 (2.5)
Not reported 11 (2.1) 8 (1.5)
Other 24 (4.6) 22 (4.2)
Multiple 1 (0.2) 0
ECOG PS score, n (%)
0 328 (62.5) 348 (66.0)
1 197 (37.5) 178 (33.8)
2 0 1 (0.2)
Median time from initial diagnosis to randomization, months (range) 4.1 (0.5-222.9) 4.0 (0.7-341.4)
  • After unblinding of the study, 208 (39.5%) patients in the placebo group without disease progression received therapy with ERLEADA plus ADT (crossover group).3
  • At the clinical cutoff date, 66.2% and 46.1% of patients in the ERLEADA and placebo groups remained on treatment, respectively.1
  • At the final analysis for rPFS (following 365 events), treatment with ERLEADA significantly improved rPFS with a 52% risk reduction in radiographic progression or death (median rPFS was NE in the ERLEADA group and 22.1 months in the placebo group; HR, 0.48; 95% CI, 0.39-0.60; P<0.001).1
    • The percentage of patients with rPFS at 24 months was 68.2% and 47.5% in the ERLEADA and placebo groups, respectively.
    • The treatment effect of ERLEADA on rPFS was consistently favorable across prespecified subgroups, including prior docetaxel use and disease volume (high volume: HR, 0.53; 95% CI, 0.41-0.67; low volume: HR, 0.36; 95% CI, 0.22-0.57).
  • At the first interim analysis for OS (following 200 deaths), treatment with ERLEADA significantly improved OS with a 33% risk reduction in death (median OS was NE in either group; HR, 0.67; 95% CI, 0.51-0.89; P=0.005).1
    • The OS percentage at 24 months was 82.4% and 73.5% in the ERLEADA and placebo groups, respectively.
    • The treatment effect on OS consistently favored ERLEADA over placebo across prespecified subgroups, with no difference based on disease volume (high volume: HR, 0.68; 95% CI, 0.50-0.92; low volume: HR, 0.67; 95% CI, 0.34-1.32).
  • Time to cytotoxic chemotherapy was significantly longer in the ERLEADA group compared with the placebo group (HR, 0.39; 95% CI, 0.27-0.56; P<0.001).1
  • Based on preplanned hierarchical testing sequence, formal significance testing was not performed for the other secondary endpoints because there was no significant difference between the groups for time to pain progression (P=0.12).1
  • The final analysis for OS was performed after 405 deaths (170 patients in the ERLEADA group and 235 patients in the placebo group) and a median follow-up of 44.0 months.1
  • An improvement in median OS was observed: NR in the ERLEADA group vs 52.2 months in the placebo group (HR, 0.65; 95% CI, 0.53-0.79; P<0.0001), with a 35% risk reduction in death. OS results did not include formal statistical inference, and the updated analyses presented for secondary endpoints were based on the final data cutoff and performed without formal statistical retesting. The final formal statistical testing for all secondary endpoints was performed at the time of the first interim analysis.3
    • Based on a prespecified sensitivity analysis for OS that accounted for ~40% crossover from the placebo group to the ERLEADA group using the IPCW log-rank test, there was a 48% risk reduction in death after adjusting for crossover (median, NR vs 39.8 months in the ERLEADA group vs placebo group; HR, 0.52; 95% CI, 0.42-0.64; P<0.0001).
    • The treatment effect of ERLEADA on OS was favorable across certain prespecified subgroups, including patients with high- and low-volume mCSPC (HR, 0.70; 95% CI, 0.56-0.88 and HR, 0.52; 95% CI, 0.35-0.79, respectively) and high-risk patients (HR, 0.57; 95% CI, 0.45-0.73). The interaction effect between treatment and the subgroup with bone metastases only at baseline was statistically significant for OS (P=0.0108).
  • At treatment discontinuation, 247 (47.0%) patients in the ERLEADA group and 345 (65.5%) patients in the placebo group were alive, of whom 36.0% (n=89) and 50.1% (n=173) received first life-prolonging subsequent therapy, respectively.3
    • Of 138 patients in the ERLEADA group and 261 patients in the placebo group who were alive and discontinued because of progressive disease, 54.3% and 57.9%, respectively, received first life-prolonging subsequent therapy, most commonly docetaxel and abiraterone acetate plus prednisone.
    • Among 109 patients in the ERLEADA group and 84 patients in the placebo group who were alive and discontinued for other reasons, 12.8% and 26.2%, respectively, also received first life-prolonging subsequent therapy.
    • Overall, of 527 patients in the placebo group, 173 (32.8%) received first life-prolonging subsequent therapy. Together with 208 (39.5%) patients in the placebo group who crossed over to receive ERLEADA, 381 (72.3%) patients in the placebo group received active life-prolonging subsequent treatment after study treatment discontinuation.
  • Median total FACT-P scores indicated HRQoL remained stable in the ERLEADA group, with no substantial differences between treatment groups. Specific HRQoL domains, measured by FACT-P subscales, were also maintained in the ERLEADA group.3,4
  • There were no significant differences between treatment groups in median TTD in any FACT-P or BPI scores.40
  • The safety population included all patients who received ≥1 dose of study drug; 1 patient in the ERLEADA group discontinued the study prior to receiving a dose.1
  • Treatment discontinuation due to progressive disease was reported in 99 (18.9%) vs 227 (43.1%) patients in the ERLEADA vs placebo group.1
  • Ischemic heart disease was reported in 4.4% vs 1.5% of patients in the ERLEADA vs placebo group; 2 patient deaths due to ischemic events were reported in each group.1
  • AEs associated with death in 10 patients in the ERLEADA group included acute kidney injury (n=2), acute MI, MI, cardiogenic shock, sudden cardiac death, cardio-respiratory arrest, respiratory failure, cerebrovascular accident, and large intestinal ulcer perforation (all n=1).37
  • AEs associated with death in 16 patients in the placebo group included sudden death (n=2), respiratory failure (n=2), acute MI, acute coronary syndrome, cardiac failure, intracranial hemorrhage, subdural hemorrhage, vascular rupture, pulmonary embolism, sepsis, urosepsis, hypothermia, suicide, and unspecified death (all n=1).37

Summary of AEs1,37

AE, n (%) ERLEADA group
(n=524) 		Placebo group
(n=527)
Any grade Grade 3-4 Any grade Grade 3-4
Any AE 507 (96.8) 221 (42.2) 509 (96.6) 215 (40.8)
Serious AE 104 (19.8) - 107 (20.3) -
AE leading to treatment discontinuationa 42 (8.0) - 28 (5.3) -
AE leading to death 10 (1.9) - 16 (3.0) -
AEs reported in ≥10% of patients or grade ≥3 in ≥10 patients in either groupb
Hot flush 119 (22.7) 0 86 (16.3) 0
Fatigue 103 (19.7) 8 (1.5) 88 (16.7) 6 (1.1)
Hypertension 93 (17.7) 44 (8.4) 82 (15.6) 48 (9.1)
Back pain 91 (17.4) 12 (2.3) 102 (19.4) 14 (2.7)
Arthralgia 91 (17.4) 2 (0.4) 78 (14.8) 5 (0.9)
Pain in arm or leg 64 (12.2) 3 (0.6) 67 (12.7) 5 (0.9)
Pruritus 56 (10.7) 1 (0.2) 24 (4.6) 1 (0.2)
Weight increased 54 (10.3) 6 (1.1) 89 (16.9) 10 (1.9)
Anemia 48 (9.2) 9 (1.7) 71 (13.5) 17 (3.2)
Constipation 47 (9.0) 0 57 (10.8) 0
Asthenia 37 (7.1) 10 (1.9) 44 (8.3) 3 (0.6)
Bone pain 34 (6.5) 6 (1.1) 53 (10.1) 9 (1.7)
Rash (generalized) 34 (6.5) 14 (2.7) 5 (0.9) 2 (0.4)
Blood ALP increased 16 (3.1) 2 (0.4) 28 (5.3) 13 (2.5)
Urinary retention 13 (2.5) 4 (0.8) 19 (3.6) 10 (1.9)

aRash was the most common AE leading to treatment discontinuation (2.3% vs 0.2%), dose reduction (5.3% vs 0.8%), and dose interruption (8.4% vs 0.9%) in the ERLEADA group vs the placebo group, respectively.
bShown are AEs of any cause that occurred from the time of the first dose of the trial intervention through 30 days after the last dose. AEs were assessed monthly and graded according to NCI CTCAE, version 4.0.3. One patient who was assigned to the ERLEADA group withdrew consent before treatment.

  • In the ERLEADA vs placebo vs crossover group, safety results are as follows3:
    • The median treatment duration was 39.3 vs 20.2 vs 15.4 months.
    • Adjusting for the difference in duration of exposure, rates of TEAEs of interest per 100 patient-years were 40.0 vs 22.4 vs 41.9.
    • Progressive disease was the most frequent reason for treatment discontinuation and was reported in 138 (26.3%) vs 245 (76.8%) vs 16 (7.7%) patients.
    • Total patient-years of exposure was 1358.9 vs 793.3 vs 243.6.
  • There were no treatment-related deaths.3

Summary of AEs3,4

AE,a n (%) ERLEADA group
(n=524)		 Placebo group
(n=527)		 Crossover group
(n=208)
All grades Grade ≥ 3 All grades Grade ≥ 3 All grades Grade ≥ 3
≥1 TEAE,b 510 (97.3) 259 (49.4) 510 (96.8) 220 (41.7) 174 (83.7) 57 (27.4)
Any serious TEAE,b 153 (29.2) - 115 (21.8) - 29 (13.9) -
Any TEAE leading to treatment discontinuation 62 (11.8) - 30 (5.7) - 16 (7.7) -
TEAE leading to death 20 (3.8) - 17 (3.2) - 7 (3.4) -
Any COVID-19 AE 0 - 0 - 3 (1.4)c -
Most frequent TEAEs (occurring in ≥10% of patients)
Back pain 108 (20.6) - 111 (21.1) - 11 (5.3) -
Arthralgia 103 (19.7) - 82 (15.6) - 15 (7.2) -
Pain in extremity 70 (13.4) - 67 (12.7) - 8 (3.8) -
Fatigue 107 (20.4) - 89 (16.9) - 15 (7.2) -
Bone pain 39 (7.4) - 54 (10.2) - 2 (1.0) -
Rash 106 (20.2) - 23 (4.4) - 26 (12.5) -
Pruritus 58 (11.1) - 25 (4.7) - 13 (6.3) -
Constipation 59 (11.3) - 58 (11.0) - 6 (2.9) -
Diarrhea 56 (10.7) - 35 (6.6) - 11 (5.3) -
Hot flush 121 (23.1) - 87 (16.5) - 3 (1.4) -
Hypertension 102 (19.5) - 84 (15.9) - 13 (6.3) -
Weight increased 55 (10.5) - 92 (17.5) - 7 (3.4) -
Anemia 69 (13.2) - 72 (13.7) - 13 (6.3) -

aShown are AEs of any cause, unless otherwise noted, that occurred from the time of the first dose of the trial intervention through 30 days after the last dose. For each category, patients with multiple events were counted only once. AEs were assessed monthly and graded according to NCI CTCAE, version 4.0.3. One patient who was assigned to the ERLEADA group withdrew consent before treatment.
bExcludes grade 5 events.
cThree patients in the crossover group reported COVID-19 TEAEs which resolved and did not lead to treatment discontinuation or death.

  • A post hoc analysis that evaluated depth of PSA reduction and long-term outcomes determined that 68% of patients achieved undetectable PSA levels (≤0.2 ng/mL) in the ERLEADA group compared with 32% in the placebo group and 90% and 73% of patients, respectively, had an overall ≥50% and ≥90% decline in PSA response in the ERLEADA group compared with 55% and 29% in the placebo group. Achievement of deep PSA decline (≥90% PSA decline or PSA≤0.2 ng/mL) at 3 months of ERLEADA initiation was associated with improved OS (HR, 0.35; 95% CI, 0.25-0.48), rPFS (HR, 0.44; 95% CI, 0.30-0.65), time to PSA progression (HR, 0.31; 95% CI, 0.22-0.44), and time to castration resistance (HR, 0.38; 95% CI, 0.27-0.52); P≤0.0001 for all. Similar results were seen at 6 and 12 months of ERLEADA initiation.10

PSA relationship to rPFS and OS

  • In another post hoc analysis that evaluated PSA kinetics (PSA50, PSA90, and PSA ≤0.2 ng/mL) and rPFS, patients in the ERLEADA group achieved PSA50, PSA90, and PSA ≤0.2 ng/mL as early as 3 months after initiation of ERLEADA, with a median time to achieve a PSA50 response of 1 month. Patients in the ERLEADA group who achieved PSA50, PSA90, and PSA ≤0.2 ng/mL were at lower risk of radiographic progression compared with patients who did not achieve these responses (median rPFS for patients in the ERLEADA group with vs without PSA50, PSA90, and PSA≤0.2 ng/mL: NR vs 18.3 months [HR, 0.27; 95% CI, 0.17-0.43], NR vs 28.7 months [HR, 0.46; 95% CI, 0.32-0.65], and NR vs 18.4 months [HR, 0.19; 95% CI, 0.14-0.27], respectively; all P<0.0001). At 6 months, the median rPFS was 18.3 months, 28.7 months, and NR for patients treated with ERLEADA who achieved a PSA response of <50%, 50% to <90%, and ≥90%, respectively.11
  • In another post hoc analysis that evaluated the relationship between depth of PSA decline and OS reported that patients in the ERLEADA group who achieved PSA50, PSA90, and PSA ≤0.2 ng/mL achieved significant improvement in OS compared with those who did not achieve these responses (median OS for patients with vs without PSA50, PSA90, and PSA ≤0.2 ng/mL, respectively, in the ERLEADA group: NR vs 35.0 months [HR, 0.38; 95% CI, 0.25-0.59], NR vs 45.2 months [HR, 0.44; 95% CI, 0.32-0.60], and NR vs 30.0 months [HR, 0.17; 95% CI, 0.13-0.23]; all P<0.0001). Shorter time to undetectable PSA (≤0.2 ng/mL) correlated with longer OS time (rank correlation, -0.5; 95% CI, -0.6 to -0.4; P<0.05).12

PSA relationship to HRQoL

  • In a post hoc analysis, rapid and deep PSA decline (defined as a decline of ≥90% from baseline or to ≤0.2 ng/mL) correlated with HRQoL measures (ie, time to worsening in FACT-P total score, worsening in FACT-P physical wellbeing subscale score, BPI-SF worst pain intensity progression, or BFI worst fatigue intensity progression) at 3 and 6 months following treatment with ERLEADA added to ADT.27

Effect of ultra-low PSA on clinical outcomes

  • In a post hoc analysis that evaluated the effect of ultra-low PSA (≤0.2 ng/mL) on clinical outcomes, the percentage of patients achieving ultra-low 1 (>0.02 to ≤0.2 ng/mL) and ultra-low 2 (≤0.02 ng/mL) PSA levels with ERLEADA vs placebo by 3 months was 38% and 23% vs 15% and 5%, respectively. Compared with patients with PSA >0.2 ng/mL, OS and rPFS were significantly improved in patients with ultra-low 1 (OS: HR, 0.46; 95% CI, 0.31-0.67; nominal P<0.001; rPFS: HR, 0.54; 95% CI, 0.35-0.83; nominal P=0.005) and ultra-low 2 (OS: HR, 0.24; 95% CI, 0.13-0.43; nominal P<0.001; rPFS: HR, 0.28; 95% CI, 0.14-0.54; nominal P<0.001) PSA at 3 months. Patients with ultra-low 2 PSA also showed significantly improved time to castration resistance (HR, 0.2; 95% CI, 0.11-0.38; nominal P<0.001) and time to PSA progression (HR, 0.11; 95% CI, 0.04-0.27; nominal P<0.001). Compared with patients with PSA >0.2 ng/mL anytime, those achieving ultra-low 2 PSA by 3 months showed improved OS, with higher HRs observed with longer time to reach ultra-low 2 PSA (3 months: HR, 0.12 [95% CI, 0.06-0.22; nominal P<0.001]; 3-6 months: HR, 0.14 [95% CI, 0.08-0.27; nominal P<0.001]; 6 months: HR, 0.25 [95% CI, 0.17-0.36; nominal P<0.001]). These endpoints were not adjusted for multiple comparisons. Therefore, the P-values displayed are nominal, and statistical significance has not been established. The overall safety profile in patients who achieved PSA decline at 3 months of study treatment is similar to a prior post hoc PSA analysis10 and overall intent-to-treat population.32

Early PSA response

  • In an exploratory secondary analysis that evaluated whether early PSA response (defined as achieving a PSA level of ≤0.2 ng/mL by 6 months of randomization) was predictive of treatment efficacy, 61% of patients in the ERLEADA group and 24% of patients in the placebo group achieved an early PSA response. The ERLEADA group was associated with improved OS in 6-month PSA responders (HR, 0.66; 95% CI, 0.44-1.00) vs nonresponders (HR, 1.14; 95% CI, 0.89-1.46), with a differential treatment effect between groups stratified by early PSA response by 6 months (P=0.03); no significant difference was observed at 3 months (P=0.17). In the ERLEADA vs placebo group, 3-year confounder-adjusted OS was 84% (80%-88%) vs 74% (66%-82%) among 6-month PSA responders and 58% (52%-65%) vs 56% (51%-60%) among nonresponders.33

Clinical outcomes based on progression status

  • In a retrospective analysis that evaluated clinical outcomes, 12.4% of patients (n=130 [ERLEADA group, n=64; placebo group, n=66]) experienced R-PD and 41.2% (n=433 [ERLEADA group, n=125; placebo group, n=308]) experienced PSA-PD. In the ERLEADA vs placebo group, median time to radiographic progression and time to PSA progression, respectively, were delayed in patients with R-PD (11 vs 3.6 months; HR, 0.51; 95% CI, 0.36-0.73; P=0.0003) and PSA-PD (HR, 0.61; 95% CI, 0.49-0.75; P<0.0001). Median OS was shorter in patients with R-PD vs PSA-PD (22.9 months [95% CI, 20.2-30.9] vs 37.4 months [95% CI, 33.7-40.3]; HR, 1.56; 95% CI, 1.22-1.99; P=0.0004).34
  • A post hoc analysis evaluated the efficacy and safety outcomes for patients with baseline high- and low-risk mCSPC.13
    • High-risk mCSPC was defined as ≥2 of the following risk factors: Gleason score of ≥8, ≥3 bone lesions, and presence of measurable visceral metastasis.
    • The treatment benefit on rPFS in the ERLEADA group was significant compared with the placebo group in both the high- and low-risk mCSPC subgroups.
    • Patients in the ERLEADA group considered high-risk at baseline had significantly improved OS following treatment as well as significantly longer PFS2 compared with the placebo group.

Efficacy results and first subsequent therapies following discontinuation for patients with high- and low-Risk mCSPC in the TITAN study13

High-risk mCSPC Low-risk mCSPC
ERLEADA
group
(n=289)		 Placebo
group
(n=286)		 ERLEADA
group
(n=236)		 Placebo
group
(n=241)
rPFS
HR (95% CI; P-value) 0.44 (0.34-0.57; <0.0001) 0.54 (0.38-0.78; 0.001)
OS
24-month survival rate, % 76 63 90 85
HR (95% CI; P-value) 0.62 (0.45-0.87; 0.005) 0.74 (0.44-1.25; 0.261)
PFS2
HR (95% CI; P-value) 0.617 (0.441-0.863; 0.005) 0.693 (0.428-1.124; 0.1351)
High-risk mCSPC Low-risk mCSPC
ERLEADA
group
(n=107)a 		Placebo
group
(n=175)a 		ERLEADA
group
(n=63)a 		Placebo
group
(n=96)a
First Subsequent Therapies
Patients with subsequent therapy, n (%)b 64 (59.8) 126 (72.0) 23 (36.5) 64 (66.7)
Abiraterone acetate plus prednisone 14 (13.1) 31 (17.7) 7 (11.1) 14 (14.6)
Docetaxel 23 (21.5) 45 (25.7) 6 (9.5) 22 (22.9)
Bicalutamide 11 (10.3) 17 (9.7) 5 (7.9) 14 (14.6)
Enzalutamide 2 (1.9) 14 (8.0) 1 (1.6) 3 (3.1)

aNumber of patients alive at treatment discontinuation.
bSome patients received subsequent therapies as a result of discontinuation due to AEs.

  • TEAEs reported in the high- and low-risk subgroups were similar regardless of disease risk and consistent with previously reported results in the overall study population.13

Safety results for patients With high- and low-risk mCSPC in the TITAN study13

AEs, n (%) High-risk mCSPC Low-risk mCSPC
ERLEADA
group
(n=289)a 		Placebo
group
(n=286)b 		ERLEADA
group
(n=235)c 		Placebo
group
(n=241)d
Patients with TEAEs 278 (96.2) 278 (97.2) 229 (97.4) 231 (95.9)
Patients with serious AEs 62 (21.5) 61 (21.3) 42 (17.9) 46 (19.1)
Drug related 6 (2.1) 2 (0.7) 4 (1.7) 2 (0.8)
Grade 3-4 49 (17.0) 49 (17.1) 35 (14.9) 37 (15.4)
Patients with drug-related TEAEs leading to treatment discontinuation 8 (2.8) 1 (0.3) 9 (3.8) 3 (1.2)
Patients with TEAEs leading to death 7 (2.4) 12 (4.2) 3 (1.3) 4 (1.7)
Drug related 0 0 0 0
All deaths within 30 days of last dose 13 (4.5) 16 (5.6) 5 (2.1) 7 (2.9)

a-dMedian treatment duration, months: a19.5; b14.7; c21.8; d20.3.

  • A post hoc analysis evaluated efficacy and safety outcomes for patients with high- and low-volume mCSPC.7
    • Results from the pre-specified analysis evaluating efficacy and safety outcomes in patients with high- and low-volume mCSPC at the primary analysis have previously been reported.8
    • At the final analysis, the treatment benefit on OS, time to PSA progression, and time to castration resistance observed in the ERLEADA group of the overall study population was additionally improved in the high- and low-volume mCSPC subgroups.7
      • Using IPCW log-rank test to account for ~40% crossover, the ERLEADA group had improvement in OS in both high- and low-volume mCSPC (high-volume: HR, 0.61; 95% CI, 0.49-0.78; P<0.0001 and low-volume: HR, 0.34; 95% CI, 0.22-0.53; P<0.0001).
    • At 3 months, PSA decline ≥50% (PSA50) and undetectable PSA (≤0.2 ng/mL) in the ERLEADA group was observed in 87% and 40% of patients with high-volume mCSPC and 93% and 68% with low-volume mCSPC, respectively.

Efficacy results for patients with high- and low-Volume mCSPC in the TITAN study7

High-volume mCSPC Low-volume mCSPC
ERLEADA
group
(n=325)		 Placebo
group
(n=335)		 ERLEADA
group
(n=200)		 Placebo
group
(n=192)
OS
Median, months NR 38.7 NR NR
HR (95% CI; P-value) 0.70 (0.56-0.88; 0.002) 0.53 (0.35-0.79; 0.002)
Time to PSA progression
Median, months NR 9.2 NR 18.5
HR (95% CI; P-value) 0.32 (0.26-0.41; <0.0001) 0.15 (0.09-0.23; <0.0001)
Time to castration resistance
Median, months NR 8.3 NR 18.5
HR (95% CI; P-value) 0.40 (0.32-0.48; <0.0001) 0.23 (0.16-0.33; <0.0001)
  • The ERLEADA safety profile in both high- and low-volume mCSPC remained consistent with previous reports.7
  • A protocol-defined and post hoc analysis evaluated efficacy and safety outcomes for patients based on disease volume (high vs low), number of metastases (oligometastases vs polymetastases), and timing of metastasis presentation (synchronous vs metachronous).30
    • Among patients in the ERLEADA group, those with oligometastatic disease (≤5 bone-only metastases) had improved rPFS and OS compared with those with polymetastatic disease (>5 bone-only metastases, >5 bone metastases plus other organ metastases, or ≤5 bone metastases plus other organ metastases).
      • Patients with polymetastatic disease involving >5 bone metastases plus metastases in other locations had the poorest outcomes.
      • Compared with patients with bone-only metastasis, OS and rPFS were shorter for patients with metastases in bone plus viscera plus other locations (OS: HR, 2.63; 95% CI, 1.68-4.10; P<0.001; rPFS: HR, 3.42; 95% CI, 2.10-5.55; P<0.001) and those with metastases in bone plus other locations (OS: HR, 1.90; 95% CI, 1.37-2.63; P<0.001; rPFS: HR, 2.22; 95% CI, 1.52-3.25; P<0.001).

Primary efficacy results in patients with different disease volume or timing of metastasis in the TITAN study30

Synchronous/
high-volume
mCSPC		 Synchronous/
low-volume
mCSPC		 Metachronous/
high-volume
mCSPC		 Metachronous/
low-volume
mCSPC
ERLEADA
(n=273)		 Placebo
(n=294)		 ERLEADA
(n=138)		 Placebo
(n=147)		 ERLEADA
(n=32)		 Placebo
(n=28)		 ERLEADA
(n=53)		 Placebo
(n=31)
rPFS
Median, months NR 15.0 NR 32.9 18.7 11.1 NR NR
HR (95% CI) 0.51 (0.39-0.66) 0.38 (0.22-0.65) 0.57 (0.27-1.24) 0.27 (0.09-0.85)
OS
Median, months NR 36.7 NR 52.2 NR 39.6 NR NR
HR (95% CI) 0.68 (0.53-0.87) 0.65 (0.40-1.05) 0.69 (0.33-1.44) 0.22 (0.09-0.55)
    • PFS2, time to PSA progression, time to castration resistance, select first subsequent life-prolonging therapy for prostate cancer after study treatment discontinuation, and confirmed best ≥50% or ≥90% PSA decline or PSA ≤0.2 ng/mL results were also reported for these patient subgroups.31
  • High-volume mCSPC subgroup TEAEs, grade 3-4 TEAEs, and serious AEs30:
    • ERLEADA group: 96%, 54%, and 29% of patients
    • Placebo group: 97%, 47%, and 22% of patients
  • Low-volume mCSPC subgroup TEAEs, grade 3-4 TEAEs, and serious AEs30:
    • ERLEADA group: 99%, 43%, and 30% of patients
    • Placebo group: 96%, 33%, and 21% of patients
  • A similar safety profile was observed across treatment groups in the synchronous or metachronous subgroups.30
    • One exception was falls and fractures, which were more common in the metachronous subgroup than in the synchronous subgroup.
  • The cumulative incidence of grade 3-4 TEAEs and serious TEAEs was similar across treatment groups, regardless of disease volume or metastatic status at diagnosis.30
  • A post hoc analysis evaluated the efficacy, safety, and PROs at the primary and final analyses in older patients, stratified by age (<65, 65-79, and ≥80 years).5
    • rPFS was analyzed at the first interim analysis, and confirmed deep PSA decline, OS, HRQoL, and safety were analyzed at the final analysis.
    • The HR for rPFS favored the ERLEADA vs placebo group for all age subgroups.
    • At the final analysis, the HR for OS favored the ERLEADA vs placebo group.

Efficacy results for patients by age subgroup in the TITAN study5

<65 years
(n=331)		 65-79 years
(n=628)		 ≥80 years
(n=93)
ERLEADA
group		 Placebo
group		 ERLEADA
group		 Placebo
group		 ERLEADA
group		 Placebo
group
rPFSa
Median, months NR 18.4 NR 23 NR NR
HR (95% CI) 0.45 (0.31-0.66) 0.51 (0.39-0.68) 0.55 (0.25-1.21)
OSb
Median, months NR 41.7 NR 52.2 NR 41.7
HR (95% CI) 0.57 (0.40-0.80) 0.70 (0.54-0.91) 0.74 (0.40-1.39)

aMedian follow-up: 22.7 months.
bMedian follow-up: 44 months.

    • The treatment effect of ERLEADA on best PSA decline by age group was evaluated using descriptive statistics, Kaplan-Meier analysis, Cox proportional hazards model, and mixed-effects model for repeated measures.
  • The median (range) treatment duration for patients <65, 65-79, and ≥80 years old in the ERLEADA group was 39.8 (1.0-52.7), 39.8 (0.0-55.7), and 23.6 (2.0-48.2) months, respectively.5
  • At the final analysis, exposure-adjusted rates of TEAEs increased with age regardless of treatment; the rates of TEAEs of interest such as skin rash, falls, and fractures increased with age in the ERLEADA vs placebo group.5

Safety results for patients by age subgroup in the TITAN study5,a

<65 years
(n=330)		 65-79 years
(n=628)		 ≥80 years
(n=93)
ERLEADA
group
(n=148) 		Placebo
group
(n=182) 		ERLEADA
group
(n=324) 		Placebo
group
(n=304) 		ERLEADA
group
(n=52) 		Placebo
group
(n=41)
Total exposure, patient-years 386 254 863 481 110 58.7
Exposure-adjusted rate, events/100 patient-yearsb
Patients with ≥1 TEAE 329 558 393 504 562 504
Patients with serious TEAEs 11.9 27.5 21.3 18.7 39.9 32.4
TEAEs leading to discontinuation 1.3 2.0 3.9 1.5 10.0 8.5
TEAEs of interest 28.5 20.1 43.3 24.8 58.0 23.9
Skin rash 19.2 10.6 26.4 8.1 27.2 8.5
Fall 2.6 5.5 4.6 7.7 14.5 6.8
Fracture 3.1 2.8 7 5.4 10 0
Ischemic heart disease 2.6 0 3.6 2.5 4.5 1.7
Ischemic cerebrovascular disorder 0.3 0.4 1.7 1.0 1.8 6.8
Seizure 0.8 0.8 0 0 0 0

aOne patient did not receive study medication.
bTEAE rates per 100 patient-years of exposure in each treatment group were calculated as: 100 × distinct events of each preferred term/total patient-year of exposure (total duration of exposure/365.25).

  • The treatment effect of ERLEADA on HRQoL by age group was evaluated using descriptive statistics, Kaplan-Meier analysis, Cox proportional hazards model, and mixed-effects model for repeated measures. HRQoL was maintained regardless of age and ERLEADA was tolerated well.5
    • Across age groups, patients receiving ERLEADA or placebo had consistent total FACT-P scores of over 5.4 years.5
    • Across age groups, per responses from FACT-P physical wellbeing question GP5 (“I am bothered by side effects of treatment”), patients receiving ERLEADA reported either not being bothered by treatment side effects over time or not being any more bothered than patients receiving placebo.6
    • Across age groups, in patients receiving ERLEADA, overall physical wellbeing and energy levels remained consistent and were comparable with those in patients receiving placebo.6
    • Per FACT-P total scores, patients aged ≥75 years with a baseline ECOG PS of 1 maintained their general HRQoL.5
  • A post hoc analysis evaluated the efficacy and safety of ERLEADA in patients with D0 or D1 mCSPC at initial diagnosis.9
    • At 22.7 months of median follow-up, treatment with ERLEADA (median OS and rPFS, NR) significantly improved OS and rPFS vs placebo (median OS, NR; median rPFS, 22.1 months) in both subgroups.
      • OS, D0: HR, 0.40; 95% CI, 0.15-1.03; P=0.0481 and D1: HR, 0.72; 95% CI, 0.53-0.98; P=0.0339
      • rPFS, D0: HR, 0.41; 95% CI, 0.22-0.77; P=0.0044 and D1: HR, 0.49; 95% CI, 0.39-0.62; P<0.0001
    • There was significantly prolonged time to PSA progression in the apalutamide group compared with the placebo group in both the D0 and D1 subgroups:
      • D0: HR, 0.26; 95% CI, 0.13‑0.50; P<0.0001
      • D1: HR, 0.26; 95% CI, 0.20-0.33; P<0.0001
  • In both the D0 and D1 subgroups, treatment in the ERLEADA group increased the percentage of patients with confirmed ≥50% and ≥90% PSA decline, shortened the time to achieve PSA decline, and increased the depth of PSA decline vs the placebo group.9

PSA kinetics in the D0 and D1 subgroups in the TITAN study9

PSA kinetics D0 D1
ERLEADA
group
(n=85) 		Placebo
group
(n=59) 		ERLEADA
group
(n=411) 		Placebo
group
(n=441)
Confirmed PSA50, n (%) 76 (89.4)a 28 (47.5) 370 (90.0)a 232 (52.4)
Confirmed PSA90, n (%) 57 (67.1)a 15 (25.4) 302 (73.5)a 103 (23.4)
Time to PSA50, months, median (range) n=76
0.95 (0.9-4.6) 		n=28
0.97 (0.7-7.4) 		n=370
0.95 (0.3-11.1) 		n=231
0.95 (0.1-16.6)
Time to PSA90, months, median (range) n=57
1.84 (0.9-11.0) 		n=15
5.59 (0.9-14.8) 		n=302
1.87 (0.3-20.3) 		n=103
2.76 (0.1-18.4)
Confirmed depth of PSA decline, n (%)
<50% 9 (10.6) 31 (52.5) 41 (10.0) 210 (47.6)
50% to <90% 19 (22.4) 13 (22.0) 68 (16.5) 128 (29.0)
≥90% 57 (67.1) 15 (25.4) 302 (73.5) 103 (23.4)

aP<0.0001.

  • The safety results were as follows9:

Summary of AEs9

AEs, % D0 D1
ERLEADA
group
(n=85) 		Placebo
group
(n=59) 		ERLEADA
group
(n=411) 		Placebo
group
(n=441)
AEs 98.8 96.6 96.4 96.4
AEs leading to treatment discontinuation 11.9 6.8 7.5 5.0
Death within 30 days of treatment dose 2.4 1.7 3.9 4.8
  • A post hoc analysis was performed to assess the impact of patient baseline comorbidities, including CV and metabolic risk factors, on PSA, rPFS, OS, and safety. Patients receiving associated concomitant medications for these risk factors were additionally analyzed.35
    • Patient distribution based on baseline CV or metabolic risk factors (eg, CV ischemia, CV failure, CV arrhythmia, diabetes, hyperlipidemia, hypertension, obesity) across all 3 subgroups in the ERLEADA vs placebo group:
      • With CV/metabolic risk factors: 72% vs 69%
      • With CV/metabolic risk factors and concomitant medications: 68% vs 66%
      • Without CV/metabolic risk factors: 28% vs 31%
    • Percentage of patients achieving PSA90 or PSA < 0.2 ng/mL was similar across all 3 subgroups.
      • With CV/metabolic risk factors: 86.2% vs 43.1%
      • With CV/metabolic risk factors and concomitant medications: 85.8% vs 42.1%
      • Without CV/metabolic risk factors: 82.3% vs 43.6%
    • Treatment with ERLEADA vs placebo significantly improved rPFS and OS regardless of baseline comorbidities or use of associated concomitant medications.

Efficacy results for patients with baseline CV or metabolic risk factors ± concomitant medications35

With CV / metabolic
risk factors		 With CV / metabolic
risk factors and
concomitant
medications		 Without CV / metabolic
risk factors
ERLEADA
group
(n=378) 		Placebo
group
(n=364) 		ERLEADA
group
(n=358) 		Placebo
group
(n=347) 		ERLEADA
group
(n=146) 		Placebo
group
(n=163)
rPFSa
HR; P-value 0.49; <0.0001 0.47; <0.0001 0.48; <0.0001
OSb
HR; P-value 0.63; 0.001 0.61; <0.0001 0.71; <0.0604

aMedian follow-up: 22.7 months.
bMedian follow-up: 44 months.

  • TEAE incidences were similar between patients with and without baseline comorbidities regardless of associated concomitant medication use.35

Summary of TEAEs35

TEAEs, n (%) With CV / metabolic
risk factors		 With CV / metabolic
risk factors and
concomitant
medications		 Without CV / metabolic
risk factors
ERLEADA
group
(n=378) 		Placebo
group
(n=364) 		ERLEADA
group
(n=358) 		Placebo
group
(n=347) 		ERLEADA
group
(n=146) 		Placebo
group
(n=163)
TEAEs 368 (97.4) 353 (97.0) 350 (97.8) 337 (97.1) 142 (97.3) 157 (96.3)
Grade 3-4 TEAEs 183 (48.4) 165 (45.3) 177 (49.4) 161 (46.4) 76 (52.1) 55 (33.7)
Serious AEs 117 (31.0) 81 (22.3) 115 (32.1) 80 (23.1) 36 (24.7) 34 (20.9)
TEAEs leading to treatment discontinuation 48 (12.7) 21 (5.8) 48 (13.4) 20 (5.8) 14 (9.6) 9 (5.5)
TEAEs leading to death 15 (4.0) 11 (3.0) 15 (4.2) 11 (3.2) 5 (3.4) 6 (3.7)
  • In a post hoc analysis evaluating PFS2 by first subsequent therapy following discontinuation of study treatment, specifically hormonal compared with taxane therapy, the ERLEADA group demonstrated a reduced risk of PFS2 compared with the placebo group, regardless of hormonal (median, NR in either group; HR, 0.684; 95% CI, 0.482-0.971; P=0.0326) or taxane (median, NR in either group; HR, 0.634; 95% CI, 0.456-0.881; P=0.0062) therapy as the first subsequent therapy.14
  • An exploratory analysis evaluated OS beyond the TITAN study follow-up for the overall population, with or without IPCW crossover adjustment, and for the low-volume disease, high-volume disease, high-volume disease synchronous, and high-volume disease metachronous subgroups. Treatment with ERLEADA (median OS, 71.5 months) vs placebo significantly improved OS by a median of 32 months in the overall population. Treatment with ERLEADA improved OS (median OS, 113.1 months) in the low-volume disease subgroup, with a consistent median OS of 52 months across the high-volume disease subgroups.15
  • A post hoc analysis of patients in the ERLEADA group showed that rPFS, OS, time to PSA progression, and ≤0.2 ng/mL PSA response were similar among patients who received and those who did not receive prior docetaxel.28
  • In another analysis that evaluated the pharmacokinetics and relationship between ERLEADA exposure and selected clinical efficacy and safety observations, treatment in the ERLEADA group was found to be efficacious in extending the rPFS and OS compared with the placebo group. No statistical association was observed between rPFS, OS, and ERLEADA exposure quartiles within a relatively narrow ERLEADA exposure range (coefficient of variation, 22%). Patients with increased ERLEADA exposure reported an increased incidence of skin rash and pruritus.29
  • A descriptive post hoc analysis was conducted to evaluate the incidence of thrombotic and embolic TEAEs in patients who did or did not receive concomitant OACs in the ERLEADA and placebo groups. The occurrence of thrombotic and embolic TEAEs was similar between the ERLEADA and placebo groups in the overall safety population (4.2% vs 3.8%) and in the subgroups that did (19.4% vs 21.4%) or did not (3.2% vs 2.8%) receive anticoagulants, respectively.26
  • Additional analyses evaluating the effect of prior prostate-directed local therapy on ERLEADA therapy response, association between PSA progression and radiographic progression, molecular signatures, subtypes, and androgen receptor activity and aberrations with long-term outcomes have been reported.16-22 There have additionally been patient subgroup analyses conducted for Latin American, Japanese, and East Asian patients enrolled in the TITAN study.23-25,37
ADT Androgen deprivation therapy MI Myocardial infarction
AE Adverse event MRI Magnetic resonance imaging
ALP Alkaline phosphatase NCI CTCAE National Cancer Institute Common Terminology Criteria for Adverse Events
BFI Brief Fatigue Inventory NE Not estimable
BPI-SF Brief Pain Inventory-Short Form NR Not reached
CI Confidence interval OAC Oral anticoagulant
COVID-19 Coronavirus Disease 2019 OS Overall survival
CRPC Castration-resistant prostate cancer PCWG2 Prostate Cancer Working Group 2
CT Computed tomography PFS2 Second progression-free survival
CV Cardiovascular PO Orally
D0 Progression to mCSPC after localized disease PRO Patient-reported outcome
D1 De novo mCSPC PSA Prostate-specific antigen
ECOG PS Eastern Cooperative Oncology Group Performance Status PSA50 PSA decline of ≥50%
EuroQoL EQ-5D-5L 5-level version of the European Quality of Life-5 Dimensions PSA90 PSA decline of ≥90%
FACT-P Functional Assessment of Cancer Therapy-Prostate PSA-PD PSA progression without prior radiographic progression
GnRH Gonadotropin-releasing hormone R-PD Radiographic progression without PSA progression
HR Hazard ratio RECIST Response Evaluation Criteria In Solid Tumors
HRQoL Health-related quality of life rPFS Radiographic progression-free survival
IDMC Independent data-monitoring committee SMQ Standardized MedDRA Query
IPCW Inverse probability censoring weighted TEAE Treatment-emergent adverse event
mCSPC Metastatic castration-sensitive prostate cancer TTD Time to deterioration
MedDRA Medical Dictionary for Regulatory Activities

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 30 January 2025.

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  2. Chi KN, Agarwal N, Bjartell A, et al. Protocol for: Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019;381(1):13-24.
  3. Chi KN, Chowdhury S, Bjartell A, et al. Apalutamide in patients with metastatic castration-sensitive prostate cancer: final survival analysis of the randomized, double-blind, phase III TITAN study. J Clin Oncol. 2021;39(20):2294-2303.
  4. Chi KN, Chowdhury S, Bjartell A, et al. Supplement for: Apalutamide in patients with metastatic castration-sensitive prostate cancer: final survival analysis of the randomized, double-blind, phase III TITAN study. J Clin Oncol. 2021;39(20):2294-2303.
  5. Shen J, Chowdhury S, Agarwal N, et al. Apalutamide efficacy, safety and wellbeing in older patients with advanced prostate cancer from phase 3 randomised clinical studies TITAN and SPARTAN. Br J Cancer. 2024;130(1):73-81.
  6. Shen J, Chowdhury S, Agarwal N, et al. Supplement for: Apalutamide efficacy, safety and wellbeing in older patients with advanced prostate cancer from phase 3 randomised clinical studies TITAN and SPARTAN. Br J Cancer. 2024;130(1):73-81.
  7. Chowdhury S, Bjartell A, Merseburger AS, et al. Apalutamide for metastatic castration-sensitive prostate cancer: outcomes in high-volume and low-volume disease from the TITAN final analysis. Poster presented at: 36th Annual European Association of Urology (EAU) Congress Virtual Meeting; July 8-12, 2021.
  8. Uemura H, Ha Chung B, Ye D, et al. Apalutamide for metastatic castration-sensitive prostate cancer in TITAN: outcomes in patients with high- and low-volume disease. Oral Presentation presented at: Japan Society of Clinical Oncology (JSCO) Annual Meeting; October 24-26, 2019; Fukuoka, Japan.
  9. Bjartell A, Ye D, Agarwal N, et al. Apalutamide plus androgen deprivation therapy for metastatic castration-sensitive prostate cancer (mCSPC) in TITAN: outcomes in patients with de novo (D1) mCSPC vs progression to mCSPC after localized disease (D0) at diagnosis. Poster presented at: 35th Annual European Association of Urology (EAU) Congress Virtual Meeting; July 17-26, 2020.
  10. Chowdhury S, Bjartell A, Agarwal N, et al. Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer. Ann Oncol. 2023;34(5):477-485.
  11. Chi KN, Saad F, Chowdhury S, et al. Prostate-specific antigen kinetics in patients with advanced prostate cancer treated with apalutamide: results from the TITAN and SPARTAN studies. Poster presented at: American Society of Clinical Oncology (ASCO) 20 Virtual Scientific Program; May 29-31, 2020.
  12. Chi KN, Saad F, Chowdhury S, et al. Prostate-specific antigen kinetics in patients with advanced prostate cancer treated with apalutamide: results from the TITAN and SPARTAN studies. Oral Presentation presented at: The 2021 American Urological Association (AUA) Annual Meeting; September 10-13, 2021; Virtual Meeting.
  13. Ozguroglu M, Chowdhury S, Bjartell A, et al. Apalutamide for metastatic castration-sensitive prostate cancer in TITAN: outcomes in patients with low- and high-risk disease. Poster presented at: 2020 Genitourinary Cancers Symposium; February 13-15, 2020; San Francisco, CA.
  14. Agarwal N, Chowdhury S, Bjartell A, et al. Time to second progression (PFS2) in patients from TITAN with metastatic castration-sensitive prostate cancer by first subsequent therapy (hormonal vs taxane). Oral Presentation presented at: 2020 Genitourinary Cancers Symposium; February 13-15, 2020; San Francisco, CA.
  15. Agarwal N, Bjartell A, Juárez A, et al. Estimating median overall survival of apalutamide compared with placebo in metastatic hormone-sensitive prostate cancer (mHSPC) populations: statistical extrapolations of the TITAN study. Poster presented at: American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium; January 25-27, 2024; San Francisco, CA.
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  17. Fukuokaya W, Yanagisawa T, Mori K, et al. Radiographic progression without corresponding prostate-specific antigen progression in patients with metastatic castration-sensitive prostate cancer receiving apalutamide: secondary analysis of the TITAN trial. [published online ahead of print April 29, 2024]. Eur Urol Oncol. doi: 10.1016/j.euo.2024.04.009.
  1. Bjartell A, Agarwal N, Karsh LI, et al. Relationships of sites and burden of metastases with long-term outcomes and molecular subtypes in TITAN. Poster presented at: The 2021 American Urological Association (AUA) Annual Meeting; September 10-13, 2021; Virtual Meeting.
  2. Feng FY, Thomas S, Aguilar-Bonavides C, et al. Molecular determinants of outcome for metastatic castration-sensitive prostate cancer with addition of apalutamide or placebo to androgen deprivation therapy in TITAN. Poster presented at: American Society of Clinical Oncology (ASCO) 20 Virtual Scientific Program; May 29-31, 2020.
  3. Lucas J, Agarwal N, Feng F, et al. Molecular signatures associated with long-term response to apalutamide in patients with metastatic castration-sensitive prostate cancer in TITAN. Poster presented at: American Association for Cancer Research (AACR) 2021 Virtual Meeting; April 10-15, 2021.
  4. Chi KN, Thomas S, Gormley M, et al. Androgen receptor and non-androgen receptor aberrations associated with outcomes in metastatic castration-sensitive prostate cancer treated with apalutamide plus androgen deprivation therapy in TITAN. Poster presented at: American Association for Cancer Research (AACR) 2020 Virtual Meeting II; June 22-24, 2020.
  5. Agarwal N, Lucas J, Bonavides CA, et al. Genomic aberrations associated with overall survival (OS) in metastatic castration-sensitive prostate cancer (mCSPC) treated with apalutamide (APA) or placebo (PBO) plus androgen deprivation therapy (ADT) in TITAN. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022; Chicago, IL and online.
  6. Juarez A, Chi KN, Pereira AJ, et al. Latin American patient subgroup analysis of the phase 3 TITAN study: apalutamide plus ADT in metastatic hormone-sensitive prostate cancer (mHSPC). Poster presented at: American Association for Cancer Research (AACR) 2021 Virtual Meeting; April 10-15, 2021.
  7. Uemura H, Arai G, Uemura H, et al. Safety and efficacy of apalutamide in Japanese patients with metastatic castration-sensitive prostate cancer receiving androgen deprivation therapy: final report for the Japanese subpopulation analysis of the randomized, placebo-controlled, phase III TITAN study. Int J Urol. 2022;29(6):533-540.
  8. Chung BH, Huang J, Uemura H, et al. Apalutamide for metastatic castration-sensitive prostate cancer: final analysis of the Asian subpopulation in the TITAN trial. Asian J Androl. 2023;25(6):653-661.
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