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 castration-resistant prostate cancer (CRPC) or metastatic castration-sensitive prostate cancer (mCSPC).1

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

Learn more about the XTANDI MOA

XTANDI is taken as 160 mg (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 should be swallowed whole. Instruct patients 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

LHRH, luteinizing hormone-releasing hormone.

Learn more about XTANDI dosing and administration

In the data from the 4 randomized placebo-controlled trials, the most 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 most 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 for the treatment of prostate cancer by the2-4:

  • National Comprehensive Cancer Network (NCCN®)
  • American Urological Association (AUA)
  • American Society of Clinical Oncology (ASCO)

Learn more about XTANDI in clinical guidelines

XTANDI Support Solutions® provides:

  • 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* vs placebo + LHRH therapy* 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

Learn more about the ARCHES trial study design

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* vs placebo + LHRH therapy* (HR = 0.39 [95% CI, 0.30-0.50]; P < 0.0001).1

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

Overall survival data were not mature at the time of radiographic progression-free survival analysis (7.3% of deaths in the intent-to-treat-population had been reported).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 most 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* vs placebo + LHRH therapy* in 1401 patients with nmCRPC who had progressed on LHRH therapy*.1,6

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.6

Learn more about the PROSPER trial study design

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 (HR = 0.29 [95% CI, 0.24-0.35]; P < 0.0001).1

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

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 efficacy results

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* vs placebo + LHRH therapy* in 1199 patients who had received prior docetaxel-based chemotherapy.1,7

LHRH, luteinizing hormone-releasing hormone.

*Or after bilateral orchiectomy.1

Learn more about the AFFIRM trial study design

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

Median overall survival for 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, sinusitus, 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* vs placebo + LHRH therapy* in 1717 patients with mCRPC who had not undergone chemotherapy and who were asymptomatic or mildly symptomatic.1,8

LHRH, luteinizing hormone-releasing hormone.

*Or after bilateral orchiectomy.1

Learn more about the PREVAIL trial study design

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

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.8,9

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* vs placebo + LHRH therapy* (HR = 0.77 [95% CI, 0.67-0.88]).1

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

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.

*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-pathological 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, sinusitus, 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* vs bicalutamide + LHRH therapy* in 375 patients with mCRPC who were asymptomatic or mildly symptomatic and had not received prior chemotherapy.1,10

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

*Or after bilateral orchiectomy.1

Learn more about the TERRAIN trial study design

The primary endpoint of the TERRAIN trial was progression-free survival.10

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.10

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* vs bicalutamide + LHRH therapy* (HR = 0.60 [95% CI, 0.43‑0.83]).1

Median radiographic progression-free survival was 19.5 months (95% CI, 11.8-NR) for patients receiving XTANDI + LHRH therapy* vs 13.4 months (95% CI, 8.2-16.4) for 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 study, 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, sinusitus, 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. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.1.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed 03-16-2020. To view the most recent and complete version of the guideline, go online to NCCN.org. 3. American Urological Association. Castration-resistant prostate cancer: AUA guideline (05-2018). https://www.auanet.org/guidelines/prostate-cancer-castration-resistant-guideline (2013, amended 2018). Accessed 03-31-2020. 4. Basch E, Loblaw DA, Oliver TK, et al. Systemic therapy in men with metastatic castration-resistant prostate cancer: American Society of Clinical Oncology and Cancer Care Ontario clinical practice guideline. J Clin Oncol 2014;32(30):3436-48. 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. 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. 7. 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. 8. Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 2014;371(5):424-33. 9. 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. 10. 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 0.5% of patients receiving XTANDI in seven 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 seven 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 four randomized, placebo-controlled clinical studies, ischemic heart disease occurred more commonly in patients on the XTANDI arm compared to patients on the placebo arm (2.9% vs 1.3%). Grade 3-4 ischemic events occurred in 1.4% of patients on XTANDI versus 0.7% 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 four randomized, placebo-controlled clinical studies, falls occurred in 11% of patients treated with XTANDI compared to 4% of patients treated with placebo. Fractures occurred in 10% of patients treated with XTANDI and in 4% 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 four randomized placebo-controlled trials, the most common ARs ( 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 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 adverse events (AEs) 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 AEs 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 AE as the primary reason were reported for 8% of XTANDI patients and 6% of bicalutamide patients.

In PROSPER, the placebo-controlled study of non-metastatic CRPC (nmCRPC) patients, Grade 3 or higher ARs were reported in 31% of XTANDI patients and 23% of placebo patients. Discontinuations with an AE 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 AEs were reported in 24% of XTANDI-treated patients. Permanent discontinuation due to AEs as the primary reason was reported in 5% of XTANDI patients and 4% of placebo patients.

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 neutrophil count decreased, white blood cell decreased, hyperglycemia, hypermagnesemia, hyponatremia, and hypercalcemia.

Hypertension: In the combined data from four randomized placebo-controlled clinical trials, hypertension was reported in 12% of XTANDI patients and 5% of placebo patients. Hypertension led to study discontinuation in < 1% of patients in each arm.

Drug Interactions

Effect of Other Drugs on XTANDI Avoid strong CYP2C8 inhibitors, as they can increase the plasma exposure to XTANDI. If co-administration is necessary, reduce the dose of XTANDI.

Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to XTANDI. If co-administration is necessary, increase the dose of XTANDI.

Effect of XTANDI on Other Drugs Avoid CYP3A4, CYP2C9, and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

Indications

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

  • castration-resistant prostate cancer (CRPC)
  • metastatic castration-sensitive prostate cancer (mCSPC)

Please see Full Prescribing Information.

Important Safety Information

Warnings and Precautions

Seizure occurred in 0.5% of patients receiving XTANDI in seven 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 seven 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 four randomized, placebo-controlled clinical studies, ischemic heart disease occurred more commonly in patients on the XTANDI arm compared to patients on the placebo arm (2.9% vs 1.3%). Grade 3-4 ischemic events occurred in 1.4% of patients on XTANDI versus 0.7% 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 four randomized, placebo-controlled clinical studies, falls occurred in 11% of patients treated with XTANDI compared to 4% of patients treated with placebo. Fractures occurred in 10% of patients treated with XTANDI and in 4% 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 four randomized placebo-controlled trials, the most common ARs ( 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 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 adverse events (AEs) 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 AEs 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 AE as the primary reason were reported for 8% of XTANDI patients and 6% of bicalutamide patients.

In PROSPER, the placebo-controlled study of non-metastatic CRPC (nmCRPC) patients, Grade 3 or higher ARs were reported in 31% of XTANDI patients and 23% of placebo patients. Discontinuations with an AE 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 AEs were reported in 24% of XTANDI-treated patients. Permanent discontinuation due to AEs as the primary reason was reported in 5% of XTANDI patients and 4% of placebo patients.

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 neutrophil count decreased, white blood cell decreased, hyperglycemia, hypermagnesemia, hyponatremia, and hypercalcemia.

Hypertension: In the combined data from four randomized placebo-controlled clinical trials, hypertension was reported in 12% of XTANDI patients and 5% of placebo patients. Hypertension led to study discontinuation in < 1% of patients in each arm.

Drug Interactions

Effect of Other Drugs on XTANDI Avoid strong CYP2C8 inhibitors, as they can increase the plasma exposure to XTANDI. If co-administration is necessary, reduce the dose of XTANDI.

Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to XTANDI. If co-administration is necessary, increase the dose of XTANDI.

Effect of XTANDI on Other Drugs Avoid CYP3A4, CYP2C9, and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

Indications

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

  • castration-resistant prostate cancer (CRPC)
  • metastatic castration-sensitive prostate cancer (mCSPC)

Please see Full Prescribing Information.