This site is intended for US healthcare providers only.
Important Safety Information Full Prescribing Information (PI) Patient Website
Important Safety Information Full Prescribing Information (PI) Patient Website
This site is intended for US healthcare providers only.
XTANDI is indicated for the treatment of patients with nonmetastatic castration-sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR), metastatic castration-sensitive prostate cancer (mCSPC), or castration-resistant prostate cancer (CRPC).1

EFFICACY RESULTS IN CSPC

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ARCHES Trial

XTANDI + GnRH therapy* significantly extended radiographic progression-free survival†1

ARCHES assessed the efficacy and safety of XTANDI + GnRH therapy* vs placebo + GnRH therapy* in patients with mCSPC.1

In a mCSPC study: Radiographic Progression-Free Survival (primary endpoint from primary analysis): 61% reduction in the risk of radiographic disease progression or death with XTANDI® + GnRH therapy* (n = 574) vs placebo + GnRH therapy* (n = 576) (HR = 0.39 [95% CI, 0.30-0.50]; P < 0.0001)
  • Number of events: 89 (15.5%) with XTANDI + GnRH therapy* vs 198 (34.4%) with placebo + GnRH therapy*1
  • Median: NR in XTANDI + GnRH therapy* (95% CI, NR-NR) vs 19.4 months with placebo + GnRH therapy* (95% CI, 16.6 months-NR)1
  • Consistent radiographic progression-free survival results were observed in patients with low and high‡ volume of disease and patients with and without prior docetaxel therapy1

See mCSPC (ARCHES) adverse reactions

*Or after bilateral orchiectomy.1

†Radiographic progression-free survival was defined as the time from randomization to radiographic disease progression at any time or death within 24 weeks after study drug discontinuation.1

‡Defined as metastases involving the viscera or, in the absence of visceral lesions, ≥ 4 bone lesions, ≥ 1 of which must be in a bony structure beyond the vertebral column and pelvic bone.1

View Study Design

ARCHES assessed the efficacy and safety of XTANDI + GnRH therapy* vs placebo + GnRH therapy* in patients with mCSPC1

mCSPC Chart
  • Baseline patient characteristics included1:
    • 66% of patients had a Gleason score of ≥ 8
    • 12% of patients received concomitant bone-targeted agents (bisphosphonates or RANKL inhibitors), which included both prostate and non-prostate cancer indications
    • ECOG Performance Status of 0 (78%) or 1 (22%)
  • Treatment duration: treatment continued until radiographic disease progression,∥ start of new treatment, unacceptable toxicity, or withdrawal1
  • Exclusion criteria included predisposing factors for seizure and clinically significant cardiovascular disease3

*Or after bilateral orchiectomy.1

†Defined as metastases involving the viscera or, in the absence of visceral lesions, ≥ 4 bone lesions, ≥ 1 of which must be in a bony structure beyond the vertebral column and pelvic bone.1

‡In ARCHES, after unblinding, 184 patients (31.9%) randomly assigned to placebo + GnRH therapy* remained progression free and consented to crossover, 180 (31.3%) of whom received treatment with XTANDI + GnRH therapy.* The median time to crossover was 21.5 months.4

§Radiographic progression-free survival was defined as the time from randomization to radiographic disease progression at any time or death within 24 weeks after study drug discontinuation.1

∥Radiographic disease progression was defined by identification of ≥ 2 new bone lesions on a bone scan with confirmation (PCWG2 criteria) and/or progression in soft-tissue disease.1

Close Study Design

XTANDI + GnRH therapy* significantly extended overall survival†1

In a mCSPC study: Overall survival (key secondary endpoint: 34% reduction in the risk of death with XTANDI® (enzalutamide + GnRH therapy* (n=574) vs placebo + GnRH therapy* (n=576). (HR = 0.66 [95% CI, 0.53-0.81]; P < 0.0001)
  • Number of events: 154 (26.8%) with XTANDI + GnRH therapy* vs 202 (35.1%) with placebo + GnRH therapy*1
  • Median: NR in XTANDI + GnRH therapy* (95% CI, NR-NR) vs NR with placebo + therapy* (95% CI, 49.7 months-NR)1
  • Data shown in graph above at 24, 36, and 48 months are according to Kaplan-Meier calculations. This was not a prespecified analysis and is not in the US Full Prescribing Information for XTANDI4

*Or after bilateral orchiectomy.1

†In ARCHES, after unblinding, 184 patients (31.9%) randomly assigned to placebo + GnRH therapy* remained progression free and consented to crossover, 180 (31.3%) of whom received treatment with XTANDI + GnRH therapy.* The median time to crossover was 21.5 months.4

5-year post-hoc overall survival follow-up analysis5

The information below is not included in the USPI for XTANDI. There was no assessment of statistical significance for this post-hoc analysis; it was not alpha-protected and should be understood as descriptive information.

In a post hoc follow up analysis of a mCSPC study: At 5 years, 66% of patients randomized to XTANDI® (enzalutamide) + GnRH therapy* and 53% of patients randomized to placebo + GnRH therapy* were alive
  • Number of events: 191 (33.3%) with XTANDI + GnRH therapy* and 223 (38.7%) with placebo + GnRH therapy*5
  • At 60 months, 66% of patients randomized to XTANDI + GnRH therapy* and 53% of patients randomized to placebo + GnRH therapy* were alive according to Kaplan-Meier calculations5
  • The median follow-up was 61.4 months5

*Or after bilateral orchiectomy.1

†In ARCHES, after unblinding, 184 patients (31.9%) randomly assigned to placebo + GnRH therapy* remained progression free and consented to crossover, 180 (31.3%) of whom received treatment with XTANDI + GnRH therapy.* The median time to crossover was 21.5 months.4

OVERALL SURVIVAL SUBGROUP ANALYSES

The information below is not included in the US Full Prescribing Information for XTANDI. Subgroups were prespecified but not alpha protected and should be considered exploratory analyses. These subgroup analyses are presented for descriptive purposes and cannot be interpreted as a demonstration of efficacy in any particular subgroup.

XTANDI® (enzalutamide) ARCHES subgroup analyses for overall survival

*Or after bilateral orchiectomy.1

†In ARCHES, after unblinding, 184 patients (31.9%) randomly assigned to placebo + GnRH therapy* remained progression free and consented to crossover, 180 (31.3%) of whom received treatment with XTANDI + GnRH therapy.* The median time to crossover was 21.5 months.4

PSA PROGRESSION

PSA: a marker you and your patients can track

PSA is not a reliable surrogate for overall survival. PSA evaluation should be viewed in the context of patient management and the overall physical condition and clinical course of the patient.

PSA undetectable rate was defined as the percentage of patients with undetectable (< 0.2 ng/mL) PSA values at any time during study treatment of those patients with detectable (≥ 0.2 ng/mL) PSA values at baseline.6

Primary Analysis: Secondary Endpoint

Patients who achieved undetectable PSA (< 0.2 ng/mL) at any time point during the primary analysis6

At any time point during the primary analysis, patients who achieved undetectable PSA (< 0.2 ng/mL)

Data cutoff October 14, 2018.6

*Or after bilateral orchiectomy.3

†N is of the intent-to-treat population for those with detectable PSA at baseline.6

Primary Analysis: Secondary Measure

The information below is not included in the USPI for XTANDI. Undetectable PSA rates at 3 months were a prespecified analysis but not alpha-controlled, and should be understood as descriptive information.

3-month PSA rate is based on patients with evaluable PSA at this time period.

Patients with undetectable PSA (< 0.2 ng/mL) at 3 months6,7

At 3 months, patients achieving undetectable PSA (< 0.2 ng/mL)

Data cutoff October 14, 2018.6

*Or after bilateral orchiectomy.3

†N is of the intent-to-treat population for those with detectable PSA at baseline.6

Time to PSA progression was also evaluated in patients with mCSPC2

The information below is not included in the USPI for XTANDI. PSA is not a reliable surrogate for overall survival. PSA evaluation should be viewed in the context of patient management and the overall physical condition and clinical course of the patient.

In a mCSPC study: XTANDI® (enzalutamide) + GnRH therapy time to PSA progression (key secondary endpoint from primary analysis)
  • Number of events: 45 (7.84%) with XTANDI + GnRH therapy† and 189 (32.81%) with placebo + GnRH therapy†6

*Time to PSA progression was defined as the time from randomization to PSA progression, which was a ≥ 25% increase and an absolute increase of ≥ 2 µg/L (≥ 2 ng/mL) above the nadir (ie, the lowest PSA value observed post baseline or at baseline), which was confirmed by a second consecutive value at least 3 weeks later.3

†Or after bilateral orchiectomy.1

PSA undetectable rate was defined as the percentage of patients with undetectable (< 0.2 ng/mL) PSA values at any time during study treatment of those patients with detectable (≥ 0.2 ng/mL) PSA values at baseline.6

A post-hoc analysis of time to PSA progression was performed at the time of final overall survival analysis4,8

The information below is not included in the USPI for XTANDI. An update to the analysis of time to PSA progression was performed at the time of the final overall survival analysis. There was no assessment of statistical significance for this post-hoc analysis, and it should be understood as descriptive information.

XTANDI® (enzalutamide) plus GnRH therapy time to PSA progression in ITT population (post-hoc analysis)
  • Number of events: 117 (20.4%) with XTANDI + GnRH therapy† and 259 (45.0%) with placebo + GnRH therapy†6

*Time to PSA progression was defined as the time from randomization to PSA progression, which was a ≥ 25% increase and an absolute increase of ≥ 2 µg/L (≥ 2 ng/mL) above the nadir (ie, the lowest PSA value observed post baseline or at baseline), which was confirmed by a second consecutive value at least 3 weeks later.3

†Or after bilateral orchiectomy.1

‡In ARCHES, after unblinding, 184 patients (31.9%) randomly assigned to placebo + GnRH therapy† remained progression free and consented to crossover, 180 (31.3%) of whom received treatment with XTANDI + GnRH therapy.† The median time to crossover was 21.5 months.4

Key secondary endpoint from primary analysis: time to deterioration of urinary symptoms*6

Treatment with XTANDI + GnRH therapy† was not associated with a statistically significant change in the time to deterioration of urinary symptoms compared with placebo + GnRH therapy† (HR = 0.88 [95% CI, 0.72-1.08]; P = 0.2162).‡

*A deterioration in urinary symptoms was defined as an increase in the urinary symptoms subscale score by ≥ 50% of the standard deviation observed in the urinary symptoms subscale score at baseline.2

†Or after bilateral orchiectomy.1

‡This information is not included in the USPI for XTANDI.

TIME TO START OF NEW ANTINEOPLASTIC THERAPY

XTANDI + GnRH therapy* significantly prolonged time to initiation of new antineoplastic therapy† in patients with mCSPC1

In a mCSPC study: Time to start of new antineoplastic therapy (key secondary endpoint from primary analysis): 72% reduction in the risk of starting a new antineoplastic therapy with XTANDI® (enzalutamide) + GnRH therapy* (n=574) vs placebo + GnRH therapy* (n=576). (HR = 0.28 [95% CI, 0.20-0.40]; P < 0.0001)

*Or after bilateral orchiectomy.1

†Time to start of new antineoplastic therapy was defined as the time from randomization to the initiation of antineoplastic therapy subsequent to the study treatments.6

An updated analysis of time to start of new antineoplastic therapy was performed at the time of final overall survival analysis4

The information below is not included in the USPI for XTANDI. An update to the analysis of time to start of new antineoplastic therapy was performed at the time of the final overall survival analysis. There was no assessment of statistical significance for this updated analysis, and it should be understood as descriptive information.

In a mCSPC study: XTANDI® (enzalutamide) plus GnRH therapy updated time to start of new antineoplastic therapy

Data cutoff May 28, 2021.4

  • Number of events: 131 (22.82%) with XTANDI + GnRH therapy† and 236 (40.97%) with placebo + GnRH therapy†6

Time to start of new antineoplastic therapy was defined as the time from randomization to the initiation of antineoplastic therapy subsequent to the study treatments.6

*For the analysis of time to start of new antineoplastic therapy, crossover to XTANDI after the primary radiographic progression-free survival analysis was not counted as a subsequent therapy.8

†Or after bilateral orchiectomy.1

‡In ARCHES, after unblinding, 184 patients (31.9%) randomly assigned to placebo + GnRH therapy† remained progression free and consented to crossover, 180 (31.3%) of whom received treatment with XTANDI + GnRH therapy.† The median time to crossover was 21.5 months.4

TIME TO CASTRATION RESISTANCE

Time to castration resistance was also evaluated in patients with mCSPC9

The information below is not included in the USPI for XTANDI. This secondary endpoint was prespecified but not alpha protected and should be considered descriptive information.

XTANDI® (enzalutamide) plus GnRH therapy time to castration resistance (other secondary endpoint from primary analysis)

Data cutoff October 14, 2018.6

  • Number of events: 90 (15.68%) with XTANDI + GnRH therapy* and 257 (44.62%) with placebo + GnRH therapy*6

Time to castration resistance was defined as the time from randomization to the first castration-resistant event (radiographic disease progression, PSA progression, or symptomatic skeletal event with castrate levels of testosterone [< 50 ng/dL]), whichever occurred first.9

*Or after bilateral orchiectomy.1

A post-hoc analysis of time to castration resistance was performed at the time of final overall survival analysis4,8

The information below is not included in the US Full Prescribing Information for XTANDI. An update to the analysis of time to castration resistance was performed at the time of the final overall survival analysis. There was no assessment of statistical significance for this post-hoc analysis, and it should be understood as descriptive information.

XTANDI® (enzalutamide) plus GnRH therapy time to castration resistance in ITT population (other secondary endpoint) post-hoc analysis

Data cutoff May 28, 2021.4

  • Number of events: 202 (35.2%) with XTANDI + GnRH therapy* and 327 (56.8%) with placebo + GnRH therapy*6

*Or after bilateral orchiectomy.1

†In ARCHES, after unblinding, 184 patients (31.9%) randomly assigned to placebo + GnRH therapy* remained progression free and consented to crossover, 180 (31.3%) of whom received treatment with XTANDI + GnRH therapy.* The median time to crossover was 21.5 months.4

REVIEW MORE DATA ABOUT XTANDI IN mCSPC (ARCHES TRIAL PUBLICATION)
REVIEW MORE DATA ABOUT XTANDI IN mCSPC (ARCHES TRIAL PUBLICATION)

Armstrong AJ, Szmulewitz RZ, Petrylak DP, et al. ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2019;37(32):2974-2986. doi:10.1200/JCO.19.00799.

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EMBARK Trial

XTANDI + GnRH therapy* significantly improved metastasis-free survival vs placebo + GnRH therapy*1

EMBARK was a randomized phase 3 trial that assessed the efficacy and safety of XTANDI + GnRH therapy* vs placebo + GnRH therapy* in 1068 patients with nmCSPC with high-risk BCR.1,2

In a nmCSPC high-risk BCR study: Metastasis-free survival (primary endpoint): 58% reduction in the risk of metastasis or death with XTANDI® (enzalutamide + GnRH therapy* (n=355) vs placebo + GnRH therapy* (n=358). (HR = 0.42. [95% CI, 0.30-0.61; P < 0.0001)
  • Number of events: 45 (12.7%) with XTANDI + GnRH therapy* vs 92 (25.7%) with placebo + GnRH therapy*1
  • Median metastasis-free survival was not reached in either the XTANDI + GnRH therapy* arm or the placebo + GnRH therapy* arm1
  • The 5-year metastasis-free survival was 87% in the XTANDI + GnRH therapy* arm and 71% in the placebo + GnRH therapy* arm. This time point was not prespecified and is not in the US Full Prescribing Information for XTANDI1,2

See nmCSPC with high-risk BCR (EMBARK) adverse reactions

*Leuprolide.1

View Study Design

The EMBARK trial assessed the efficacy and safety of XTANDI with or without GnRH therapy* vs placebo + GnRH therapy* in patients with nmCSPC with high-risk BCR1

EMBARK study design: The EMBARK trial assessed the efficacy and safety of XTANDI with or without GnRH therapy* vs placebo + GnRH therapy* in patients with nmCSPC with high-risk BCR1

In the EMBARK trial, patients were required to have nonmetastatic disease by BICR, high-risk BCR (defined by a PSA doubling time ≤ 9 months), and PSA values ≥ 1 ng/mL if they had prior RP (with or without RT) as the primary treatment for prostate cancer or PSA values ≥ 2 ng/mL above the nadir if they had prior RT only.1

*Leuprolide.1

†All treatment arms were eligible for treatment suspension. In the XTANDI + GnRH therapy* and placebo + GnRH therapy* arms, GnRH therapy* was also suspended.1

‡Study treatment was suspended once at Week 37 if PSA was < 0.2 ng/mL at Week 36; treatment was reinitiated when PSA values increased to ≥ 2.0 ng/mL for patients with prior prostatectomy or ≥ 5.0 ng/mL for patients without prior prostatectomy.1

Patient demographics and baseline characteristics were balanced between the 3 treatment arms2

XTANDI® (enzalutamide) + GnRH EMBARK patient demographics

Percentages may not total 100 because of rounding.

*Leuprolide.1

†Race or ethnic group was reported by the patients. The "Other" category includes patients who identified as multiple races or ethnic groups.2

‡ECOG Performance Status scores range from 0 to 5, with higher scores indicating greater disability.2

§PSA doubling time at baseline was calculated on the basis of a sequence of PSA values tested over time during the enrollment period. Some baseline PSA doubling time values exceeded the enrollment threshold of less than 9 months owing to discrepancies in the PSA values captured in the case-report forms as compared with the values used for the enrollment calculation.2

Close Study Design

XTANDI (single agent) significantly improved metastasis-free survival vs placebo + GnRH therapy*1

In a nmCSPC high-risk BCR study: Metastasis-free survival (key secondary endpoint): 37% reduction in the risk of metastasis or death with XTANDI® (enzalutamide (single agent) (n=355) vs placebo + GnRH therapy* (n=358). (HR = 0.63 [95% CI, 0.46-0.87]; P<0.0049)
  • Number of events: 63 (17.7%) with XTANDI (single agent) vs 92 (25.7%) with placebo + GnRH therapy*1
  • Median metastasis-free survival was not reached in either the XTANDI (single agent) arm or the placebo + GnRH therapy* arm1
  • The 5-year metastasis-free survival was 80% in the XTANDI (single agent) arm and 71% in the placebo + GnRH therapy* arm. This endpoint was not prespecified and is not in the US Full Prescribing Information for XTANDI1,2

*Leuprolide.1

XTANDI + GnRH therapy* significantly extended overall survival1,4

In a nmCSPC with high-risk BCR study: Time to start of new antineoplastic therapy was also assessed with XTANDI® (enzalutamide) + GnRH therapy vs placebo + GnRH therapy in patients with nmCSPC with high-risk BCR
  • Number of events: 73 (20.6%) with XTANDI + GnRH therapy* and 111 (31.0%) with placebo + GnRH therapy*1
  • The median follow-up time was 94.2 months with XTANDI + GnRH therapy* and 94.0 months with placebo + GnRH therapy*4
  • At 8 years, 79% of patients randomized to XTANDI + GnRH therapy* and 70% of patients randomized to placebo + GnRH therapy* were alive according to Kaplan-Meier calculations4

OVERALL SURVIVAL – XTANDI (SINGLE AGENT)4

The overall survival analysis between patients treated with XTANDI (single agent) and placebo + GnRH therapy* was not statistically significant (HR = 0.83 [95% CI, 0.63-1.10]; P = NS).4

*Leuprolide.1

OVERALL SURVIVAL SUBGROUP ANALYSES (XTANDI + GnRH THERAPY*)

Subgroups were prespecified but not alpha protected and should be considered exploratory analyses. These subgroup analyses are presented for descriptive purposes and cannot be interpreted as a demonstration of efficacy in any particular subgroup. Certain subgroups were not included in these analyses due to small numbers of events. The information below is not included in the USPI for XTANDI.

Overall Survival Key Secondary Chart

*Leuprolide.1

TIME TO START OF NEW ANTINEOPLASTIC THERAPY

This endpoint was a prespecified, alpha-protected, key secondary endpoint. There is overlap of events between time to start of new antineoplastic therapy and metastasis-free survival, because patients with new metastases are generally started on a new antineoplastic drug. Hormonal therapy was the most frequent subsequent therapy received and accounted for approximately a quarter of patients who received any subsequent therapy. Less frequent subsequent therapies included cytotoxic therapies, prostate cancer vaccines, or systemic radiopharmaceuticals. This information should be considered when evaluating the clinical importance of this analysis. This information is not included in the USPI for XTANDI.

Time to start of new antineoplastic therapy was also assessed with XTANDI + GnRH therapy* vs placebo + GnRH therapy*2,5

Time to Start Antineoplastic Therapy Chart
  • Number of events: 58 (16%) with XTANDI + GnRH therapy* and 140 (39%) with placebo + GnRH therapy*2
  • Median time to start of new antineoplastic therapy was not reached in the XTANDI + GnRH therapy* arm and was 76.2 months in the placebo + GnRH therapy* arm5

Time to start of new antineoplastic therapy was defined as the time from randomization to first use of a new antineoplastic therapy for prostate cancer. Subsequent prostate cancer therapies included hormonal therapies, cytotoxic therapies, prostate cancer vaccines, or systemic radiopharmaceuticals for prostate cancer.6

*Leuprolide.1

TREATMENT SUSPENSION

Treatment* was suspended if PSA dropped to undetectable at 36 weeks1

For patients whose PSA was undetectable (< 0.2 ng/mL) at Week 36, treatment* was suspended at Week 37 and then reinitiated when PSA increased to ≥ 2.0 ng/mL for patients with prior prostatectomy or ≥ 5.0 ng/mL for patients without prior prostatectomy.1

Primary Analysis: Secondary Measure

In a nmCSPC with high-risk BCR study: Patients who had drug treatment suspension at week 37 due to undetectable PSA during EMBARK
  • Approximately 91% of patients in the XTANDI + GnRH therapy† arm reached undetectable PSA levels (< 0.2 ng/mL) at 9 months1

Primary Analysis: Secondary Measure

In a nmCSPC with high-risk BCR study: Median duration of treatment suspension during EMBARK

Data cutoff January 31, 2023.2

  • Median treatment suspension duration in the XTANDI + GnRH therapy† arm due to undetectable PSA (< 0.2 ng/mL) at 36 weeks was 18 months1

*All treatment arms were eligible for treatment suspension. In the XTANDI + GnRH therapy† and placebo + GnRH therapy† arms, GnRH therapy† was also suspended.1

†Leuprolide.1

REVIEW MORE DATA ABOUT XTANDI IN nmCSPC WITH HIGH-RISK BCR (EMBARK TRIAL PUBLICATION)
REVIEW MORE DATA ABOUT XTANDI IN nmCSPC WITH HIGH-RISK BCR (EMBARK TRIAL PUBLICATION)

Freedland SJ, de Almeida Luz M, De Giorgi U, et al. Improved outcomes with enzalutamide in biochemically recurrent prostate cancer. N Engl J Med. 2023;389(16):1453-1465. Erratum in: N Engl J Med. 2025;393(8):832. doi:10.1056/NEJMoa2303974.

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ABOUT CSPC
EXPLORE SAFETY
EXPLORE SAFETY

BCR, biochemical recurrence; BICR, blinded independent central review; CI, confidence interval; CSPC, castration-sensitive prostate cancer; ECOG, Eastern Cooperative Oncology Group; GnRH, gonadotropin-releasing hormone; HR, hazard ratio; mCSPC, metastatic castration-sensitive prostate cancer; MFS, metastasis-free survival; nmCSPC, nonmetastatic castration-sensitive prostate cancer; NR, not reached; NS, not significant; PSA, prostate-specific antigen; RP, radical prostatectomy; RT, radiotherapy; USPI, US Full Prescribing Information.

References: 1. XTANDI. Package insert. Northbrook, IL: Astellas Pharma US, Inc; 2026. 2. Freedland SJ, de Almeida Luz M, De Giorgi U, et al. Improved outcomes with enzalutamide in biochemically recurrent prostate cancer. N Engl J Med. 2023;389(16):1453-1465. Erratum in: N Engl J Med. 2025;393(8):832. doi:10.1056/NEJMoa2303974. 3. Freedland SJ, De Giorgi U, Gleave M, et al. A phase 3 randomised study of enzalutamide plus leuprolide and enzalutamide monotherapy in high-risk non-metastatic hormone-sensitive prostate cancer with rising PSA after local therapy: EMBARK study design [published online August 12, 2021]. BMJ Open. 2021. Accessed February 5, 2025. https://bmjopen.bmj.com/content/bmjopen/11/8/e046588.full.pdf. 4. Shore ND, de Almeida Luz M, De Giorgi U, et al. Improved survival with enzalutamide in biochemically recurrent prostate cancer [published online ahead of print October 19, 2025]. N Engl J Med. 2025. Accessed October 20, 2025. https://www.nejm.org/doi/full/10.1056/NEJMoa2510310. 5. Astellas and Pfizer. XTANDI. Data on File. 6. Supplement to: Freedland SJ, de Almeida Luz M, De Giorgi U, et al. Improved outcomes with enzalutamide in biochemically recurrent prostate cancer. N Engl J Med. 2023;389(16):1453-1465. Erratum in: N Engl J Med. 2025;393(8):832. doi:10.1056/NEJMoa2303974.

CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; FDA, U.S. Food and Drug Administration; GnRH, gonadotropin-releasing hormone; HR, hazard ratio; ITT, intent to treat; mCSPC, metastatic castration-sensitive prostate cancer; NE, not evaluable; nmCSPC, nonmetastatic castration-sensitive prostate cancer; NR, not reached; PSA, prostate-specific antigen; RANKL, receptor activator of nuclear factor; USPI, US Full Prescribing Information.

References: 1. XTANDI. Package insert. Northbrook, IL: Astellas Pharma US, Inc; 2026. 2. Armstrong AJ, Szmulewitz RZ, Petrylak DP, et al. ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2019;37(32):2974-2986. doi:10.1200/JCO.19.00799. 3. Protocol for: Armstrong AJ, Szmulewitz RZ, Petrylak DP, et al. ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2019;37(32):2974-2986. doi:10.1200/JCO.19.00799. 4. Armstrong AJ, Azad AA, Iguchi T, et al. Improved survival with enzalutamide in patients with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2022;40(15):1616-1622. doi:10.1200/JCO.22.00193. 5. Armstrong AJ, Petrylak DP, Shore ND, et al. ARCHES 5-year survival with enzalutamide plus androgen-deprivation therapy in metastatic hormone-sensitive prostate cancer patients. Eur Urol. 2026;89(5):396-403. doi: 10.1016/j.eururo.2025.12.021. 6. Astellas and Pfizer. XTANDI. Data on File. 7. Azad AA, Petrylak DP, Iguchi T, et al. Enzalutamide and prostate-specific antigen levels in metastatic prostate cancer: a secondary analysis of the ARCHES randomized clinical trial [published online May 7, 2025]. JAMA Netw Open. 2025. Accessed June 23, 2026. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2833622#250312149. 8. Supplement to: Armstrong AJ, Azad AA, Iguchi T, et al. Improved survival with enzalutamide in patients with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2022;40(15):1616-1622. doi:10.1200/JCO.22.00193. 9. Supplement to: Armstrong AJ, Szmulewitz RZ, Petrylak DP, et al. ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2019;37(32):2974-2986. doi:10.1200/JCO.19.00799.

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AstellasAnswers.com

Indications

XTANDI (enzalutamide) is indicated for the treatment of patients with:

  • metastatic castration-sensitive prostate cancer (mCSPC)
  • nonmetastatic castration-sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR)
  • castration-resistant prostate cancer (CRPC)

Important Safety Information

Important Safety Information

Warnings and Precautions

Seizure occurred in 0.6% of patients receiving XTANDI in eight randomized clinical trials. In a study of patients with predisposing factors for seizure, 2.2% of XTANDI-treated patients experienced a seizure. It is unknown whether anti-epileptic medications will prevent seizures with XTANDI. Patients in the study had one or more of the following predisposing factors: use of medications that may lower the seizure threshold, history of traumatic brain or head injury, history of cerebrovascular accident or transient ischemic attack, and Alzheimer’s disease, meningioma, or leptomeningeal disease from prostate cancer, unexplained loss of consciousness within the last 12 months, history of seizure, presence of a space occupying lesion of the brain, history of arteriovenous malformation, or history of brain infection. Advise patients of the risk of developing a seizure while taking XTANDI and of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Posterior Reversible Encephalopathy Syndrome (PRES) There have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder that can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.

Hypersensitivity reactions, including edema of the face (0.5%), tongue (0.1%), or lip (0.1%) have been observed with XTANDI in eight randomized clinical trials. Pharyngeal edema has been reported in post-marketing cases. Advise patients who experience any symptoms of hypersensitivity to temporarily discontinue XTANDI and promptly seek medical care. Permanently discontinue XTANDI for serious hypersensitivity reactions.

Ischemic Heart Disease In the combined data of five randomized, placebo-controlled clinical studies, ischemic heart disease occurred more commonly in patients on the XTANDI arm compared to patients on the placebo arm (3.5% vs 2%). Grade 3-4 ischemic events occurred in 1.8% of patients on XTANDI versus 1.1% on placebo. Ischemic events led to death in 0.4% of patients on XTANDI compared to 0.1% on placebo. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue XTANDI for Grade 3-4 ischemic heart disease.

Falls and Fractures occurred in patients receiving XTANDI. Evaluate patients for fracture and fall risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents. In the combined data of five randomized, placebo-controlled clinical studies, falls occurred in 12% of patients treated with XTANDI compared to 6% of patients treated with placebo. Fractures occurred in 13% of patients treated with XTANDI and in 6% of patients treated with placebo.

Embryo-Fetal Toxicity The safety and efficacy of XTANDI have not been established in females. XTANDI can cause fetal harm and loss of pregnancy when administered to a pregnant female. Advise males with female partners of reproductive potential to use effective contraception during treatment with XTANDI and for 3 months after the last dose of XTANDI.

Dysphagia or Choking Severe dysphagia or choking, including events that could be life-threatening requiring medical intervention or fatal, can occur due to XTANDI product size. Advise patients to take each capsule or tablet whole with a sufficient amount of water to ensure that all medication is successfully swallowed. Consider use of a smaller tablet size of XTANDI in patients who have difficulty swallowing. Discontinue XTANDI for patients who cannot swallow capsules or tablets.

Interference with Immunoassay Measurement of Digoxin XTANDI can interfere with certain digoxin immunoassays (e.g., Chemiluminescent Microparticle Immunoassays), resulting in falsely elevated digoxin plasma concentration results. Notify the laboratory conducting the digoxin plasma concentration assay to use an appropriate method in patients receiving XTANDI and digoxin.

Adverse Reactions (ARs)

In the data from the five randomized placebo-controlled trials, the most common ARs (≥ 10%) that occurred more frequently (≥ 2% over placebo) in XTANDI-treated patients were musculoskeletal pain, fatigue, hot flush, constipation, decreased appetite, diarrhea, hypertension, hemorrhage, fall, fracture, and headache. In the bicalutamide-controlled study, the most common ARs (≥ 10%) reported in XTANDI-treated patients were asthenia/fatigue, back pain, musculoskeletal pain, hot flush, hypertension, nausea, constipation, diarrhea, upper respiratory tract infection, and weight loss.

In AFFIRM, the placebo-controlled study of metastatic CRPC (mCRPC) patients who previously received docetaxel, Grade 3 and higher ARs were reported among 47% of XTANDI-treated patients. Discontinuations due to ARs were reported for 16% of XTANDI-treated patients. In PREVAIL, the placebo-controlled study of chemotherapy-naive mCRPC patients, Grade 3-4 ARs were reported in 44% of XTANDI patients and 37% of placebo patients. Discontinuations due to ARs were reported for 6% of XTANDI-treated patients. In TERRAIN, the bicalutamide-controlled study of chemotherapy-naive mCRPC patients, Grade 3-4 ARs were reported in 39% of XTANDI patients and 38% of bicalutamide patients. Discontinuations with an AR as the primary reason were reported for 8% of XTANDI patients and 6% of bicalutamide patients.

In PROSPER, the placebo-controlled study of nonmetastatic CRPC (nmCRPC) patients, Grade 3 or higher ARs were reported in 31% of XTANDI patients and 23% of placebo patients. Discontinuations with an AR as the primary reason were reported for 9% of XTANDI patients and 6% of placebo patients.

In ARCHES, the placebo-controlled study of metastatic CSPC (mCSPC) patients, Grade 3 or higher ARs were reported in 24% of XTANDI-treated patients. Permanent discontinuation due to ARs as the primary reason was reported in 5% of XTANDI patients and 4% of placebo patients.

In EMBARK, the placebo-controlled study of nonmetastatic CSPC (nmCSPC) with high-risk biochemical recurrence (BCR) patients, Grade 3 or higher adverse reactions during the total duration of treatment were reported in 46% of patients treated with XTANDI plus leuprolide, 50% of patients receiving XTANDI as a single agent, and 43% of patients receiving placebo plus leuprolide. Permanent treatment discontinuation due to adverse reactions during the total duration of treatment as the primary reason was reported in 21% of patients treated with XTANDI plus leuprolide, 18% of patients receiving XTANDI as a single agent, and 10% of patients receiving placebo plus leuprolide.

Lab Abnormalities: Lab abnormalities that occurred in ≥ 5% of patients, and more frequently (> 2%) in the XTANDI arm compared to placebo in the pooled, randomized, placebo-controlled studies are hemoglobin decrease, neutrophil count decreased, white blood cell decreased, hyperglycemia, hypermagnesemia, hyponatremia, hypophosphatemia, and hypercalcemia.

Hypertension: In the combined data from five randomized placebo-controlled clinical trials, hypertension was reported in 14.2% of XTANDI patients and 7.4% of placebo patients. Hypertension led to study discontinuation in < 1% of patients in each arm.

Drug Interactions

Effect of Other Drugs on XTANDI Avoid coadministration with strong CYP2C8 inhibitors. If coadministration cannot be avoided, reduce the dosage of XTANDI.

Avoid coadministration with strong CYP3A4 inducers. If coadministration cannot be avoided, increase the dosage of XTANDI.

Effect of XTANDI on Other Drugs Avoid coadministration with certain CYP3A4, CYP2C9, and CYP2C19 substrates for which minimal decrease in concentration may lead to therapeutic failure of the substrate. If coadministration cannot be avoided, increase the dosage of these substrates in accordance with their Prescribing Information. In cases where active metabolites are formed, there may be increased exposure to the active metabolites.

Indications

XTANDI (enzalutamide) is indicated for the treatment of patients with:

  • metastatic castration-sensitive prostate cancer (mCSPC)
  • nonmetastatic castration-sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR)
  • castration-resistant prostate cancer (CRPC)

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Indications

XTANDI (enzalutamide) is indicated for the treatment of patients with:

Important Safety Information

Important Safety Information

Warnings and Precautions

Seizure occurred in 0.6% of patients receiving XTANDI in eight randomized clinical trials. In a study of patients with predisposing factors for seizure, 2.2% of XTANDI-treated patients experienced a seizure. It is unknown whether anti-epileptic medications will prevent seizures with XTANDI. Patients in the study had one or more of the following predisposing factors: use of medications that may lower the seizure threshold, history of traumatic brain or head injury, history of cerebrovascular accident or transient ischemic attack, and Alzheimer’s disease, meningioma, or leptomeningeal disease from prostate cancer, unexplained loss of consciousness within the last 12 months, history of seizure, presence of a space occupying lesion of the brain, history of arteriovenous malformation, or history of brain infection. Advise patients of the risk of developing a seizure while taking XTANDI and of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Posterior Reversible Encephalopathy Syndrome (PRES) There have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder that can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.

Hypersensitivity reactions, including edema of the face (0.5%), tongue (0.1%), or lip (0.1%) have been observed with XTANDI in eight randomized clinical trials. Pharyngeal edema has been reported in post-marketing cases. Advise patients who experience any symptoms of hypersensitivity to temporarily discontinue XTANDI and promptly seek medical care. Permanently discontinue XTANDI for serious hypersensitivity reactions.

Ischemic Heart Disease In the combined data of five randomized, placebo-controlled clinical studies, ischemic heart disease occurred more commonly in patients on the XTANDI arm compared to patients on the placebo arm (3.5% vs 2%). Grade 3-4 ischemic events occurred in 1.8% of patients on XTANDI versus 1.1% on placebo. Ischemic events led to death in 0.4% of patients on XTANDI compared to 0.1% on placebo. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue XTANDI for Grade 3-4 ischemic heart disease.

Falls and Fractures occurred in patients receiving XTANDI. Evaluate patients for fracture and fall risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents. In the combined data of five randomized, placebo-controlled clinical studies, falls occurred in 12% of patients treated with XTANDI compared to 6% of patients treated with placebo. Fractures occurred in 13% of patients treated with XTANDI and in 6% of patients treated with placebo.

Embryo-Fetal Toxicity The safety and efficacy of XTANDI have not been established in females. XTANDI can cause fetal harm and loss of pregnancy when administered to a pregnant female. Advise males with female partners of reproductive potential to use effective contraception during treatment with XTANDI and for 3 months after the last dose of XTANDI.

Dysphagia or Choking Severe dysphagia or choking, including events that could be life-threatening requiring medical intervention or fatal, can occur due to XTANDI product size. Advise patients to take each capsule or tablet whole with a sufficient amount of water to ensure that all medication is successfully swallowed. Consider use of a smaller tablet size of XTANDI in patients who have difficulty swallowing. Discontinue XTANDI for patients who cannot swallow capsules or tablets.

Interference with Immunoassay Measurement of Digoxin XTANDI can interfere with certain digoxin immunoassays (e.g., Chemiluminescent Microparticle Immunoassays), resulting in falsely elevated digoxin plasma concentration results. Notify the laboratory conducting the digoxin plasma concentration assay to use an appropriate method in patients receiving XTANDI and digoxin.

Adverse Reactions (ARs)

In the data from the five randomized placebo-controlled trials, the most common ARs (≥ 10%) that occurred more frequently (≥ 2% over placebo) in XTANDI-treated patients were musculoskeletal pain, fatigue, hot flush, constipation, decreased appetite, diarrhea, hypertension, hemorrhage, fall, fracture, and headache. In the bicalutamide-controlled study, the most common ARs (≥ 10%) reported in XTANDI-treated patients were asthenia/fatigue, back pain, musculoskeletal pain, hot flush, hypertension, nausea, constipation, diarrhea, upper respiratory tract infection, and weight loss.

In AFFIRM, the placebo-controlled study of metastatic CRPC (mCRPC) patients who previously received docetaxel, Grade 3 and higher ARs were reported among 47% of XTANDI-treated patients. Discontinuations due to ARs were reported for 16% of XTANDI-treated patients. In PREVAIL, the placebo-controlled study of chemotherapy-naive mCRPC patients, Grade 3-4 ARs were reported in 44% of XTANDI patients and 37% of placebo patients. Discontinuations due to ARs were reported for 6% of XTANDI-treated patients. In TERRAIN, the bicalutamide-controlled study of chemotherapy-naive mCRPC patients, Grade 3-4 ARs were reported in 39% of XTANDI patients and 38% of bicalutamide patients. Discontinuations with an AR as the primary reason were reported for 8% of XTANDI patients and 6% of bicalutamide patients.

In PROSPER, the placebo-controlled study of nonmetastatic CRPC (nmCRPC) patients, Grade 3 or higher ARs were reported in 31% of XTANDI patients and 23% of placebo patients. Discontinuations with an AR as the primary reason were reported for 9% of XTANDI patients and 6% of placebo patients.

In ARCHES, the placebo-controlled study of metastatic CSPC (mCSPC) patients, Grade 3 or higher ARs were reported in 24% of XTANDI-treated patients. Permanent discontinuation due to ARs as the primary reason was reported in 5% of XTANDI patients and 4% of placebo patients.

In EMBARK, the placebo-controlled study of nonmetastatic CSPC (nmCSPC) with high-risk biochemical recurrence (BCR) patients, Grade 3 or higher adverse reactions during the total duration of treatment were reported in 46% of patients treated with XTANDI plus leuprolide, 50% of patients receiving XTANDI as a single agent, and 43% of patients receiving placebo plus leuprolide. Permanent treatment discontinuation due to adverse reactions during the total duration of treatment as the primary reason was reported in 21% of patients treated with XTANDI plus leuprolide, 18% of patients receiving XTANDI as a single agent, and 10% of patients receiving placebo plus leuprolide.

Lab Abnormalities: Lab abnormalities that occurred in ≥ 5% of patients, and more frequently (> 2%) in the XTANDI arm compared to placebo in the pooled, randomized, placebo-controlled studies are hemoglobin decrease, neutrophil count decreased, white blood cell decreased, hyperglycemia, hypermagnesemia, hyponatremia, hypophosphatemia, and hypercalcemia.

Hypertension: In the combined data from five randomized placebo-controlled clinical trials, hypertension was reported in 14.2% of XTANDI patients and 7.4% of placebo patients. Hypertension led to study discontinuation in < 1% of patients in each arm.

Drug Interactions

Effect of Other Drugs on XTANDI Avoid coadministration with strong CYP2C8 inhibitors. If coadministration cannot be avoided, reduce the dosage of XTANDI.

Avoid coadministration with strong CYP3A4 inducers. If coadministration cannot be avoided, increase the dosage of XTANDI.

Effect of XTANDI on Other Drugs Avoid coadministration with certain CYP3A4, CYP2C9, and CYP2C19 substrates for which minimal decrease in concentration may lead to therapeutic failure of the substrate. If coadministration cannot be avoided, increase the dosage of these substrates in accordance with their Prescribing Information. In cases where active metabolites are formed, there may be increased exposure to the active metabolites.

Indications

XTANDI (enzalutamide) is indicated for the treatment of patients with: