Frequently Asked Questions

About XTANDI

XTANDI (enzalutamide) is an androgen receptor inhibitor that acts on multiple steps of the androgen receptor signaling pathway within the tumor cell.1

XTANDI is indicated for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC) or castration-resistant prostate cancer (CRPC).1

In preclinical studies, XTANDI inhibited androgen binding to the androgen receptor, inhibited androgen receptors from entering the nucleus, and inhibited androgen receptor binding to DNA.1

Learn more about the XTANDI MOA

XTANDI is taken as 160 mg (four 40 mg tablets, two 80 mg tablets, or four 40 mg capsules) orally, once daily.1

Administration guidelines1:

  • XTANDI can be taken at any time during the day but should be taken at the same time each day
  • XTANDI can be taken with or without food
  • Each capsule or tablet should be swallowed whole. Instruct patients not to cut, crush, or chew the tablets, and not to chew, dissolve, or open the capsules
  • If a dose of XTANDI is missed, inform patients that they should take it as soon as they remember
  • If patients forget to take their dose for the whole day, then they should take their normal dose the next day
  • Patients should not take more than their prescribed dose per day
  • Patients receiving XTANDI should also receive an LHRH analog concurrently or should have had bilateral orchiectomy

Advise patients to call their healthcare provider or go to the nearest emergency room right away if they have taken too much XTANDI. They may have an increased risk of seizure if they take too much XTANDI.1

LHRH, luteinizing hormone-releasing hormone.

Learn more about XTANDI dosing and administration

Yes, XTANDI has overall survival data in 3 disease states—mCSPC, nmCRPC, and mCRPC.1

mCSPC

At the completion of the ARCHES trial, there was 34% reduction in the risk of death in mCSPC patients treated with XTANDI + LHRH therapy* (n = 574) vs placebo + LHRH therapy* (n = 576) (HR = 0.66 [95% CI, 0.53-0.81]; P < 0.0001).1

Number of events: 154 (26.8%) with XTANDI + LHRH therapy* vs 202 (35.1%) with placebo + LHRH therapy*

Median overall survival was not reached for patients receiving XTANDI + LHRH therapy* (95% CI, NR-NR) or those receiving placebo + LHRH therapy* (95% CI, 49.7-NR).1

The primary endpoint for ARCHES was radiographic progression-free survival. Overall survival was a key secondary endpoint.1

See the recently updated final overall survival data from the ARCHES trial in mCSPC

Learn more about the ARCHES trial

nmCRPC

At the completion of the PROSPER trial, there was a 27% reduction in the risk of death in nmCRPC patients treated with XTANDI + LHRH therapy* (n = 933) vs placebo + LHRH therapy* (n = 468) (HR = 0.73 [95% CI, 0.61-0.88]; P = 0.0011).1,2

Number of events: 288 (30.9%) with XTANDI + LHRH therapy* vs 178 (38.0%) with placebo + LHRH therapy*

Median overall survival was 67.0 months (95% CI, 64.0-NR) for patients receiving XTANDI + LHRH therapy* vs 56.3 months (95% CI, 54.4-63.0) for those receiving placebo + LHRH therapy*.1,2

The primary endpoint for PROSPER was metastasis-free survival. Overall survival was a key secondary endpoint.1

The prespecified final analysis of overall survival occurred 27 months after the metastasis-free survival analysis.1

Learn more about the PROSPER trial

mCRPC

At the completion of the PREVAIL trial, there was a 23% reduction in the risk of death in pre-docetaxel patients with metastatic castration-resistant prostate cancer (mCRPC) with XTANDI + LHRH therapy* (n = 872) vs placebo + LHRH therapy* (n = 845) (HR = 0.77 [95% CI, 0.67-0.88]).1

Number of events: 368 (42%) with XTANDI + LHRH therapy* vs 416 (49%) with placebo + LHRH therapy*

Median overall survival was 35.3 months (95% CI, 32.2-NR) for patients receiving XTANDI + LHRH therapy* vs 31.3 months (95% CI, 28.8‑34.2) for those receiving placebo + LHRH therapy* (HR = 0.77 [95% CI, 0.67-0.88]).1

The co-primary endpoints for PREVAIL were radiographic progression-free survival and overall survival.1

Learn more about the PREVAIL trial

Also, in mCRPC, at the completion of the AFFIRM trial, there was a 37% reduction in risk of death for post-docetaxel patients receiving XTANDI + LHRH therapy* (n = 800) vs placebo + LHRH therapy* (n = 399) (HR = 0.63 [95% CI, 0.53-0.75]; P < 0.0001).1

Number of events: 308 (38.5%) with XTANDI + LHRH therapy* vs 212 (53.1%) with placebo + LHRH therapy*

Median overall survival for post-docetaxel patients receiving XTANDI + LHRH therapy* was 18.4 months (95% CI, 17.3-NR) vs 13.6 months (95% CI, 11.3-15.8) for those receiving placebo + LHRH therapy*.1

Learn more about the AFFIRM trial

CI, confidence interval; HR, hazard ratio; LHRH, luteinizing hormone-releasing hormone; mCRPC, metastatic castration-resistant prostate cancer; nmCRPC, nonmetastatic castration-resistant prostate cancer; NR, not reached.

*Or after bilateral orchiectomy.1

Warnings and Precautions include1:

  • Seizure occurred in 0.5% of patients receiving XTANDI. In patients with predisposing factors, seizures were reported in 2.2% of patients. Permanently discontinue XTANDI in patients who develop a seizure during treatment.
  • Posterior reversible encephalopathy syndrome (PRES): Discontinue XTANDI.
  • Hypersensitivity: Advise patients who experience hypersensitivity to temporarily discontinue XTANDI and promptly seek medical care. Permanently discontinue XTANDI for serious reactions.
  • Ischemic Heart Disease: 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: 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.
  • Embryo-Fetal Toxicity: Advise males with female partners of reproductive potential to use effective contraception.

Learn more about these Warnings and Precautions

In the data from the 4 randomized placebo-controlled trials, the common adverse reactions (≥ 10%) that occurred more frequently (≥ 2% over placebo) in XTANDI-treated patients were asthenia/fatigue, back pain, hot flush, constipation, arthralgia, decreased appetite, diarrhea, and hypertension. In the bicalutamide-controlled study, the common adverse reactions (≥ 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.1

Learn more about the XTANDI safety profile

Yes, enzalutamide (XTANDI) is recognized in the guidelines as a treatment option for mCSPC and CRPC in certain patients by the3,4:

  • National Comprehensive Cancer Network® (NCCN®)
  • American Urological Association (AUA)

Learn more about XTANDI in clinical guidelines

XTANDI Support Solutions® provides the following support to eligible patients prescribed XTANDI:

  • Benefits verification
  • Prior authorization assistance
  • Prior authorization denial appeals assistance
  • XTANDI Quick Start+® Program
  • XTANDI Patient Savings Program
  • Astellas Patient Assistance Program
  • Financial assistance information for Medicare patients

Learn more about XTANDI patient support

XTANDI treatment in mCSPC (ARCHES trial)

ARCHES was a multinational, randomized, double-blind, placebo-controlled trial of XTANDI + LHRH therapy* (n = 574) vs placebo + LHRH therapy* (n = 576) in 1150 patients with mCSPC who were stratified by prior docetaxel therapy for prostate cancer (none, 1 to 5 cycles, or 6 cycles) and disease volume (low vs high†).1,5

LHRH, luteinizing hormone-releasing hormone.

*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

The primary endpoint in the ARCHES trial was radiographic progression-free survival.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

Learn more about the ARCHES trial primary endpoint results

In the ARCHES trial, there was a 61% reduction in the risk of radiographic disease progression or death in mCSPC patients treated with XTANDI + LHRH therapy* (n = 574) vs placebo + LHRH therapy* (n = 576) (HR = 0.39 [95% CI, 0.30-0.50]; P < 0.0001).1

Number of events: 89 (15.5%) with XTANDI + LHRH therapy* vs 198 (34.4%) with placebo + LHRH therapy*

Median radiographic progression-free survival was not reached in XTANDI + LHRH therapy* (95% CI, NR-NR) vs 19.4 months with placebo + LHRH therapy* (95% CI, 16.6-NR).1

At the completion of the ARCHES trial, there was 34% reduction in the risk of death in patients treated with XTANDI + LHRH therapy* vs placebo + LHRH therapy* (HR = 0.66 [95% CI, 0.53-0.81]; P < 0.0001).1

Number of events: 154 (26.8%) with XTANDI + LHRH therapy* vs 202 (35.1%) with placebo + LHRH therapy*

Median overall survival was not reached for patients receiving XTANDI + LHRH therapy* (95% CI, NR-NR) or those receiving placebo + LHRH therapy* (95% CI, 49.7-NR).1

The prespecified final analysis of overall survival occurred 40 months after the radiographic progression-free survival analysis.6

CI, confidence interval; HR, hazard ratio; LHRH, luteinizing hormone-releasing hormone; NR, not reached.

*Or after bilateral orchiectomy.1

Learn more about the ARCHES trial efficacy results

Yes, overall survival data was a key secondary endpoint of this study.1

At the completion of the ARCHES trial, there was 34% reduction in the risk of death in mCSPC patients treated with XTANDI + LHRH therapy* (n = 574) vs placebo + LHRH therapy* (n = 576) (HR = 0.66 [95% CI, 0.53-0.81]; P < 0.0001).1

Number of events: 154 (26.8%) with XTANDI + LHRH therapy* vs 202 (35.1%) with placebo + LHRH therapy*

Median overall survival was not reached for patients receiving XTANDI + LHRH therapy* (95% CI, NR-NR) or those receiving placebo + LHRH therapy* (95% CI, 49.7-NR).1

CI, confidence interval; HR, hazard ratio; LHRH, luteinizing hormone-releasing hormone; NR, not reached.

*Or after bilateral orchiectomy.1

Learn more about the ARCHES trial efficacy results

In the ARCHES trial, the common adverse reactions that occurred at ≥ 2% higher frequency in the XTANDI arm versus placebo included hot flush (27% vs 22%), asthenic conditions (24% vs 20%)*, hypertension (8.0% vs 5.6%), fractures (6.5% vs 4.2%)†, musculoskeletal pain (6.3% vs 4.0%), decreased appetite (4.9% vs 2.6%), cognitive and memory impairment (4.5% vs 2.1%)‡, and restless legs syndrome (2.4% vs 0.3%).1

NEC, not elsewhere classifiable.

*Includes asthenia and fatigue.1

†Includes fracture-related preferred terms under high-level terms: fractures NEC; fractures and dislocations NEC; limb fractures and dislocations; pelvic fractures and dislocations; skull and brain therapeutic procedures; skull fractures, facial bone fractures and dislocations; spinal fractures and dislocations; thoracic cage fractures and dislocations.1

‡Includes memory impairment, amnesia, cognitive disorder, dementia, disturbance in attention, transient global amnesia, dementia Alzheimer’s type, mental impairment, senile dementia, and vascular dementia.1

Learn more about the ARCHES trial safety results

XTANDI treatment in nmCRPC (PROSPER trial)

PROSPER was a multinational, randomized, double-blind, placebo-controlled phase 3 trial of XTANDI + LHRH therapy* (n = 933) vs placebo + LHRH therapy* (n = 468) in 1401 patients with nmCRPC who had progressed† on LHRH therapy*.1,7

LHRH, luteinizing hormone-releasing hormone; nmCRPC, nonmetastatic castration-resistant prostate cancer; PSA, prostate-specific antigen.

*Or after bilateral orchiectomy.1

†Progression was defined as at least 3 rising PSA values (PSA1 < PSA2 < PSA3) taken at least 1 week apart despite castrate levels of testosterone (≤ 50 ng/dL) on LHRH therapy or after bilateral orchiectomy.7

The primary endpoint of the PROSPER trial was metastasis-free survival.1

Metastasis‑free survival was defined as the time from randomization to whichever of the following occurred first: 1) loco‑regional and/or distant radiographic progression per blinded independent central review; or 2) death up to 112 days after treatment discontinuation without evidence of radiographic progression.1

Learn more about the PROSPER trial primary endpoint results

In the PROSPER trial, there was a 71% reduction in the risk of metastasis or death with XTANDI + LHRH therapy* (n = 933) vs placebo + LHRH therapy* (n = 468) (HR = 0.29 [95% CI, 0.24-0.35]; P < 0.0001).1

Number of events: 219 (23.5%) with XTANDI + LHRH therapy* vs 228 (48.7%) with placebo + LHRH therapy*

Median metastasis-free survival was 3 years with XTANDI + LHRH therapy* (95% CI, 33.1-NR) vs 14.7 months with placebo + LHRH therapy* (95% CI, 14.2-15.0).1

There was a 27% reduction in the risk of death† with XTANDI + LHRH therapy* vs placebo + LHRH therapy* (HR = 0.73 [95% CI, 0.61-0.88]; P = 0.0011).1

Number of events: 288 (30.9%) with XTANDI + LHRH therapy* vs 178 (38.0%) with placebo + LHRH therapy*

Median overall survival was 67.0 months (95% CI, 64.0-NR) for patients receiving XTANDI + LHRH therapy* vs 56.3 months (95% CI, 54.4-63.0) for those receiving placebo + LHRH therapy*.1

The prespecified final analysis of overall survival occurred 27 months after the metastasis-free survival analysis.1

CI, confidence interval; HR, hazard ratio; LHRH, luteinizing hormone-releasing hormone; nmCRPC, nonmetastatic castration-resistant prostate cancer; NR, not reached.

The primary endpoint of the study was metastasis-free survival, defined as the time from randomization to whichever of the following occurred first: 1) loco-regional and/or distant radiographic progression per blinded independent central review; or 2) death up to 112 days after treatment discontinuation without evidence of radiographic progression.1

*Or after bilateral orchiectomy.1

†Overall survival was measured as the interval from randomization to death from any cause or to the date at which the patient was last known to be alive.2

Learn more about the PROSPER trial efficacy results

Yes, overall survival was a secondary endpoint of this study.1,2

At the completion of the PROSPER trial, there was a 27% reduction in the risk of death with XTANDI + LHRH therapy* vs placebo + LHRH therapy* in nmCRPC patients (HR = 0.73 [95% CI, 0.61-0.88]; P = 0.0011).1,2

Number of events: 288 (30.9%) with XTANDI + LHRH therapy* vs 178 (38.0%) with placebo + LHRH therapy*

Median overall survival was 67.0 months (95% CI, 64.0-NR) for patients receiving XTANDI + LHRH therapy* (n = 933) vs 56.3 months (95% CI, 54.4-63.0) for those receiving placebo + LHRH therapy* (n = 468).1,2

The prespecified final analysis of overall survival occurred 27 months after the metastasis-free survival analysis.1

CI, confidence interval; HR, hazard ratio; LHRH, luteinizing hormone-releasing hormone; nmCRPC, nonmetastatic castration-resistant prostate cancer; NR, not reached.

*Or after bilateral orchiectomy.1

Learn more about the PROSPER trial overall survival data

The adverse reactions reported in PROSPER that occurred at a ≥ 2% higher frequency in the XTANDI arm than in the placebo arm included asthenic conditions (40% vs 20%)*, hot flush (13% vs 7.7%), dizziness (12% vs 5.2%)†, hypertension (12% vs 5.2%), fall (11% vs 4.1%), nausea (11% vs 8.6%), fractures (9.8% vs 4.9%)‡, decreased appetite (9.6% vs 3.9%), constipation (9.1% vs 6.9%), headache (9.1% vs 4.5%), weight decreased (5.9% vs 1.5%), cognitive and attention disorders (4.6% vs 1.5%)§, and anxiety (2.8% vs 0.4%).1

*Includes asthenia and fatigue.1

†Includes dizziness and vertigo.1

‡Includes all osseous fractures from all sites.1

§Includes amnesia, memory impairment, cognitive disorder, and disturbance in attention.1

Learn more about the PROSPER trial safety results

XTANDI treatment in mCRPC
(AFFIRM trial, PREVAIL trial, TERRAIN trial)

The 3 trials that studied XTANDI in the treatment of mCRPC were1:

  • AFFIRM trial
  • PREVAIL trial
  • TERRAIN trial

mCRPC, metastatic castration-resistant prostate cancer.

AFFIRM was a multinational, randomized, double-blind, placebo-controlled phase 3 trial of XTANDI + LHRH therapy* (n = 800) vs placebo + LHRH therapy* (n = 399) in 1199 mCRPC patients who had received prior docetaxel-based chemotherapy.1,8

LHRH, luteinizing hormone-releasing hormone; mCRPC, metastatic castration-resistant prostate cancer.

*Or after bilateral orchiectomy.1

The primary endpoint of the AFFIRM trial was overall survival.8

Learn more about the AFFIRM trial primary endpoint results

In the AFFIRM trial, there was a 37% reduction in risk of death for mCRPC patients receiving XTANDI + LHRH therapy* (n = 800) vs placebo + LHRH therapy* (n = 399) (HR = 0.63 [95% CI, 0.53-0.75]; P < 0.0001).1

Number of events: 308 (38.5%) with XTANDI + LHRH therapy* vs 212 (53.1%) with placebo + LHRH therapy*1

Median overall survival for mCRPC patients receiving XTANDI + LHRH therapy* was 18.4 months (95% CI, 17.3-NR) vs 13.6 months (95% CI, 11.3-15.8) for those receiving placebo + LHRH therapy*.1

CI, confidence interval; HR, hazard ratio; LHRH, luteinizing hormone-releasing hormone; mCRPC, metastatic castration-resistant prostate cancer; NR, not reached.

*Or after bilateral orchiectomy.1

Learn more about the AFFIRM trial efficacy results

The adverse reactions reported in AFFIRM that occurred at a ≥ 2% higher frequency in the XTANDI arm compared to the placebo arm included asthenic conditions (51% vs 44%)*, back pain (26% vs 24%), diarrhea (22% vs 18%), arthralgia (21% vs 17%), hot flush (20% vs 10%), musculoskeletal pain (15% vs 12%), peripheral edema (15% vs 13%), headache (12% vs 5.5%), upper respiratory tract infection (11% vs 6.5%)†, muscular weakness (9.8% vs 6.8%), dizziness (9.5% vs 7.5%)‡, insomnia (8.8% vs 6.0%), lower respiratory tract and lung infection (8.5% vs 4.8%)§, spinal cord compression and cauda equina syndrome (7.4% vs 4.5%), hematuria (6.9% vs 4.5%), paresthesia (6.6% vs 4.5%), anxiety (6.5% vs 4.0%), hypertension (6.4% vs 2.8%), pollakiuria (4.8% vs 2.5%), fall (4.6% vs 1.3%), mental impairment disorders (4.3% vs 1.8%)||, hypoesthesia (4.0% vs 1.8%), non-pathologic fractures (4.0% vs 0.8%), pruritus (3.8% vs 1.3%), dry skin (3.5% vs 1.3%), epistaxis (3.3% vs 1.3%), and musculoskeletal stiffness (2.6% vs 0.3%).1

*Includes asthenia and fatigue.1

†Includes nasopharyngitis, upper respiratory tract infection, sinusitis, rhinitis, pharyngitis, and laryngitis.1

‡Includes dizziness and vertigo.1

§Includes pneumonia, lower respiratory tract infection, bronchitis, and lung infection.1

|| Includes amnesia, memory impairment, cognitive disorder, and disturbance in attention.1

Learn more about the AFFIRM trial safety results

PREVAIL was a multinational, randomized, double-blind, placebo-controlled phase 3 trial of XTANDI + LHRH therapy* (n = 872) vs placebo + LHRH therapy* (n = 845) in 1717 patients with mCRPC who had not undergone chemotherapy and who were asymptomatic or mildly symptomatic.1,9

LHRH, luteinizing hormone-releasing hormone; mCRPC, metastatic castration-resistant prostate cancer.

*Or after bilateral orchiectomy.1

The co-primary endpoints of the PREVAIL trial were overall survival and radiographic progression-free survival.1,9

Radiographic progression-free survival was defined as the time from randomization to the first objective evidence of radiologic progression or death due to any cause, whichever occurred first.10

Learn more about the PREVAIL trial co-primary endpoints results

In the PREVAIL trial, there was a 23% reduction in the risk of death with XTANDI + LHRH therapy* (n = 872) vs placebo + LHRH therapy* (n = 845) (HR = 0.77 [95% CI, 0.67-0.88]).1

Number of events: 368 (42%) with XTANDI + LHRH therapy* vs 416 (49%) with placebo + LHRH therapy*

Median overall survival was 35.3 months (95% CI, 32.2-NR) for patients receiving XTANDI + LHRH therapy* vs 31.3 months (95% CI, 28.8‑34.2) for those receiving placebo + LHRH therapy* (HR = 0.77 [95% CI, 0.67-0.88]).1

Also in the PREVAIL trial, there was an 83% reduction in the risk of radiographic disease progression or death with XTANDI + LHRH therapy* vs placebo + LHRH therapy* (HR = 0.17 [95% Cl, 0.14-0.21]; P < 0.0001).1

Number of events: 118 (14%) with XTANDI + LHRH therapy* vs 320 (40%) with placebo + LHRH therapy*

Median radiographic progression-free survival was not reached (95% CI, 13.8-NR) with XTANDI + LHRH therapy* vs 3.7 months (95% CI, 3.6-4.6) with placebo + LHRH therapy* (HR = 0.17 [95% CI, 0.14-0.21]; P < 0.0001).1

CI, confidence interval; HR, hazard ratio; LHRH, luteinizing hormone-releasing hormone; NR, not reached.

*Or after bilateral orchiectomy.1

Learn more about the PREVAIL trial efficacy results

The adverse reactions reported in PREVAIL that occurred at a ≥ 2% higher frequency in the XTANDI arm compared to the placebo arm included asthenic conditions (47% vs 33%)*, back pain (29% vs 22%), constipation (23% vs 17%), arthralgia (21% vs 16%), decreased appetite (19% vs 16%), hot flush (18% vs 7.8%), diarrhea (17% vs 14%), upper respiratory tract infection (16% vs 11%)†, hypertension (14% vs 4.1%), fall (13% vs 5.3%), peripheral edema (12% vs 8.2%), weight decreased (12% vs 8.5%), dizziness (11% vs 7.1%)‡, dyspnea (11% vs 8.5%)§, headache (11% vs 7.0%), hematuria (8.8% vs 5.8%), non-pathologic fracture (8.8% vs 3.0%), insomnia (8.2% vs 5.7%), lower respiratory tract and lung infection (7.9% vs 4.7%)||, dysgeusia (7.6% vs 3.7%), mental impairment disorders (5.7% vs 1.3%), gynecomastia (3.4% vs 1.4%), and restless legs syndrome (2.1% vs 0.4%).1

*Includes asthenia and fatigue.1

†Includes nasopharyngitis, upper respiratory tract infection, sinusitis, rhinitis, pharyngitis, and laryngitis.1

‡Includes dizziness and vertigo.1

§Includes dyspnea, exertional dyspnea, and dyspnea at rest.1

|| Includes pneumonia, lower respiratory tract infection, bronchitis, and lung infection.1

¶Includes amnesia, memory impairment, cognitive disorder, and disturbance in attention.1

Learn more about the PREVAIL trial safety results

TERRAIN was a multinational, randomized, double-blind phase 2 trial of XTANDI + LHRH therapy* (n = 184) vs bicalutamide + LHRH therapy* (n = 191) in 375 patients with mCRPC who were asymptomatic or mildly symptomatic and had not received prior chemotherapy.1,11

LHRH, luteinizing hormone-releasing hormone; mCRPC, metastatic castration-resistant prostate cancer.

*Or after bilateral orchiectomy.1

The primary endpoint of the TERRAIN trial was progression-free survival.11

Progression-free survival was defined as the time from randomization to the first progression event, which included radiographic disease progression, skeletal-related event, and initiation of a new antineoplastic therapy, or death, whichever occurred first.11

Learn more about the TERRAIN trial primary endpoint results

In the TERRAIN trial, there was a 40% reduction in risk of radiographic progression or death with XTANDI + LHRH therapy* (n = 184) vs bicalutamide + LHRH therapy* (n = 191) (HR = 0.60 [95% CI, 0.43‑0.83]).1

Number of events: 72 (39%) with XTANDI + LHRH therapy* vs 74 (39%) with placebo + LHRH therapy*1

Median radiographic progression-free survival was 19.5 months (95% CI, 11.8-NR) for mCRPC patients receiving XTANDI + LHRH therapy* vs 13.4 months (95% CI, 8.2-16.4) for mCRPC patients receiving bicalutamide + LHRH therapy*.1

CI, confidence interval; HR, hazard ratio; LHRH, luteinizing hormone-releasing hormone; mCRPC, metastatic castration-resistant prostate cancer; NR, not reached.

*Or after bilateral orchiectomy.1

Learn more about the TERRAIN trial efficacy results

In the TERRAIN trial, overall and common adverse reactions (≥ 10%) in the XTANDI arm versus bicalutamide included asthenic conditions (32% vs 23%)*, back pain (19% vs 18%), musculoskeletal pain (16% vs 14%)†, hot flush (15% vs 11%), hypertension (14% vs 7.4%), nausea (14% vs 18%), constipation (13% vs 13%), diarrhea (12% vs 9%), upper respiratory tract infection (12% vs 6.3%)‡, and weight loss (11% vs 7.9%).1

*Includes asthenia and fatigue.1

†Includes musculoskeletal pain and pain in extremity.1

‡Includes nasopharyngitis, upper respiratory tract infection, sinusitis, rhinitis, pharyngitis, and laryngitis.1

Learn more about the TERRAIN trial safety results

References: 1. XTANDI [package insert]. Northbrook, IL: Astellas Pharma US, Inc. 2. Sternberg CN, Fizazi K, Saad F, et al. Enzalutamide and survival in nonmetastatic, castration-resistant prostate cancer. N Engl J Med 2020;382(23):2197-206. 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed August 7, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 4. Lowrance W, Dreicer R, Jarrard DF, et al. Updates to advanced prostate cancer: AUA/SUO guideline (2023). J Urol 2023;209(6):1082-90. 5. 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):2974-86. 6. 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):1616-22. 7. Hussain M, Fizazi K, Saad F, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med 2018;378(26):2465-74. 8. Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012;367(13):1187-97. 9. Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 2014;371(5):424-33. 10. Protocol for: Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 2014;371(5):424-33. 11. Shore ND, Chowdhury S, Villers A, et al. Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomised, double-blind, phase 2 study. Lancet Oncol 2016;17(2):153-63.

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.

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, hyperphosphatemia, 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:

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

Please see Full Prescribing 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.

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, hyperphosphatemia, 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:

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

Please see Full Prescribing Information.