This site is intended for US healthcare providers only.
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

Understanding CSPC: the earlier states of advanced prostate cancer

View Information For

Understanding mCSPC

Patients may present with, or progress to, mCSPC, which is rising in prevalence.

In a projection based on SEER data1:

Understanding mCSPC

Based on a forward-looking model that used the Surveillance, Epidemiology and End Results (SEER) Program age-specific prostate cancer incidence rate data from 2008 to estimate prostate cancer incidence for each year from 2009 to 2020. To validate the model, the final results were compared with published estimates of prostate cancer incidence and prevalence in the United States for 2009 and 2020. The model estimates for the year 2020 are based on existing/current (2009) disease incidence, diagnosis, and treatment patterns, and reflect demographic changes in the US population over time (e.g., the impact of the baby boomer population).2

WHAT ARE THE 2 TYPES OF mCSPC?

Patients with mCSPC can be diagnosed with one of the following:

Diagnosed Table

*Definitive therapy is defined as a radical prostatectomy or radiotherapy with curative intent.2

†Or after bilateral orchiectomy.2

HOW DOES PROGNOSIS DIFFER BETWEEN THE TYPES OF mCSPC?

Patients with de novo mCSPC are estimated to have a lower relative survival rate than patients with clinically localized disease.4

A SEER analysis* estimates a lower (36.6%) 5-year relative survival rate for patients with mCSPC vs those with clinically localized prostate cancer (100%).4

Survival Rate Chart

*A retrospective analysis of SEER database, a collection of cancer incidence and survival data from population-based cancer registries covering approximately 48% of the US population, was conducted between 2014 and 2020.4,5

WHAT IS THE INCIDENCE OF mCSPC?

Newly diagnosed mCSPC cases in the United States are projected to continue increasing.6,7

Annual projected (2020-2025) incidence of newly diagnosed mCSPC.6,7

Incidence Chart

*From a 2018 study, based on age-period-cohort models and population projections of incidence data for men aged 45-94 years who were diagnosed with metastatic prostate cancer at initial clinical presentation. Estimates were based on the population-based SEER Program registries (2004-2014).6

Understanding the mechanism of disease (MOD) and implications in nmCSPC with high-risk BCR, mCSPC, and CRPC.

Mechanism of Disease

GnRH therapy and prostate cancer cell adaptation

In response to GnRH therapy, prostate cancer cells may adapt so that androgen receptor signaling continues to drive cell growth8-12

Mechanism of Disease

See how XTANDI may be able to help patients with mCSPC

View Trial Results

Understanding nmCSPC with biochemical recurrence (BCR) at high risk for metastasis

Risk for metastasis remains even after definitive therapy.*1,2

Some men may develop metastasis after definitive local therapy with radical prostatectomy (RP) or radiation (RT).1,2

High-Risk BCR

*Treatment for localized disease.

WHAT IS BCR IN nmCSPC?

BCR is defined by rising PSA without macroscopically detectable disease after the failure of definitive therapy.4

BCR may occur in patients who do not have symptoms. The definition of BCR is based on the type of prior definitive therapy, and guidelines vary slightly between the National Comprehensive Cancer Network® (NCCN®) and American Urological Association (AUA)/Society of Urologic Oncology (SUO)4,5:

What is BCR

*The NCCN Guidelines® include a third category in addition to persistent disease and PSA recurrence. The third group comprises patients with persistent, low PSA levels, attributed to either slow PSA metabolism or residual benign tissue. NCCN Guidelines suggest that this group does not require further evaluation unless PSA increases.5

†The NCCN Guidelines note that there is no consensus definition of a threshold for a truly undetectable PSA level. They recommend the option that clinicians evaluate patients with persistent disease and PSA recurrence for metastatic disease.5

HOW PREVALENT IS BCR AFTER DEFINITIVE THERAPY?

Based on 2 retrospective studies (n = 1997 and n = 304) as well as estimates of men with preoperative high-risk disease, rates of RP, and rates of BCR3,6,7:

Survival Rate Chart
WHEN IS BCR CONSIDERED HIGH RISK FOR METASTASIS?

Shorter PSA doubling time is associated with increased risk for metastasis.6,8,9

At the time of BCR in nmCSPC, PSA doubling time has been shown to be one of the most reliable indicators of the risk for further disease progression. A PSA doubling time of < 9 months has been associated with poor prognosis.8,10,11

Based on a retrospective analysis of men treated with RP at a single hospital6,8:

Median Metastasis-Free Survival
  • While patients with local recurrence have a PSA doubling time of 13 months, those with a PSA doubling time of 3 months present with distant metastases12
  • The number of patients in the above study was relatively small, requiring that the findings be viewed as preliminary8

Watch a video in which Dr. Jason Efstathiou discusses the impact of high-risk BCR on prostate cancer prognosis.

HOW IS BCR EVALUATED AS HIGH RISK IN nmCSPC?
Incidence Chart

Identifying patients with nmCSPC with high-risk BCR is an early step in prognosis and guiding the management approach3,15

WHAT ARE THE RECOMMENDATIONS TO HELP DETECT HIGH-RISK BCR EARLY?

Guidelines recommend monitoring PSA levels after definitive treatment.5

Following treatment with curative intent for localized prostate cancer, serial PSA measurements with clinical evaluation can be important during follow-up. These measurements enable the determination of PSA doubling time, which is a reliable indicator of the risk for disease progression.5,6,9-11

The options recommended for PSA testing by the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer are5:

Patients at high risk of recurrence:
Every 3 months

High Risk Calendar

Other patients: Every 6 to 12 months

Other Patients Calendar

The NCCN Guidelines® suggest the option of considering tumor stage, Gleason score, and initial PSA when determining if a patient is at high risk of recurrence.5

In this video, Dr. Daniel Petrylak discusses monitoring patients for high-risk BCR.

See Dr. Evan Goldfischer review profiles of 3 hypothetical patients with high-risk BCR

Understanding the mechanism of disease (MOD) and implications in nmCSPC with high-risk BCR, mCSPC, and CRPC.

Mechanism of Disease

GnRH therapy and prostate cancer cell adaptation

In response to GnRH therapy, prostate cancer cells may adapt so that androgen receptor signaling continues to drive cell growth.16-20

Mechanism of Disease

See how XTANDI may be able to help patients with nmCSPC with high-risk BCR

View Trial Results
CSPC HOME
EXPLORE EFFICACY

CRPC, castration-resistant prostate cancer; CSPC, castration-sensitive prostate cancer; GnRH, gonadotropin-releasing hormone; mCSPC, metastatic castration-sensitive prostate cancer; nmCSPC, nonmetastatic castration-sensitive prostate cancer; PSA, prostate-specific antigen.

References: 1. Suardi N, Porter CR, Reuther AM, et al. A nomogram predicting long-term biochemical recurrence after radical prostatectomy. Cancer. 2008;112(6):1254-1263. 2. Klusa D, Lohaus F, Furesi G, et al. Metastatic spread in prostate cancer patients influencing radiotherapy response [published online March 3, 2021]. Front Oncol. 2021. https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.627379/full. 3. Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999;281(17):1591-1597. 4. Lowrance W, Dreicer R, Jarrard DF, et al. Updates to advanced prostate cancer: AUA/SUO guideline (2023). J Urol. 2023;209(6):1082-1090. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.2.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed April 21, 2025. 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. 6. Freedland SJ, Humphreys EB, Mangold LA, et al. Risk of prostate cancer–specific mortality following biochemical recurrence after radical prostatectomy. JAMA. 2005;294(4):433-439. 7. Dess RT, Morgan TM, Nguyen PL, et al. Adjuvant versus early salvage radiation therapy following radical prostatectomy for men with localized prostate cancer [published online June 6, 2017]. Curr Urol Rep. 2017. https://link.springer.com/article/10.1007/s11934-017-0700-0. 8. Antonarakis ES, Feng Z, Trock BJ, et al. The natural history of metastatic progression in men with prostate-specific antigen recurrence after radical prostatectomy: long-term follow-up. BJU Int. 2012;109(1):32-39. 9. Lowrance W, Dreicer R, Jarrard DF, et al. Updates to advanced prostate cancer: AUA/SUO guideline (2023). J Urol. 2023;209(6):1082-1090. 10. Albertsen PC, Hanley JA, Penson DF, Fine J. Validation of increasing prostate specific antigen as a predictor of prostate cancer death after treatment of localized prostate cancer with surgery or radiation. J Urol. 2004;171(6 Pt 1):2221-2225. 11. Ward JF, Blute ML, Slezak J, Bergstralh EJ, Zincke H. The long-term clinical impact of biochemical recurrence of prostate cancer 5 or more years after radical prostatectomy. J Urol. 2003;170(5):1872-1876. 12. Hancock SL, Cox RS, Bagshaw MA. Prostate specific antigen after radiotherapy for prostate cancer: a reevaluation of long-term biochemical control and the kinetics of recurrence in patients treated at Stanford University. J Urol. 1995;154(4):1412-1417. 13. Antonarakis ES, Chen Y, Elsamanoudi SI, et al. Long-term overall survival and metastasis-free survival for men with prostate-specific antigen-recurrent prostate cancer after prostatectomy: analysis of the Center for Prostate Disease Research National Database. BJU Int. 2011;108(3):378-385. 14. Freedland SJ, Sutter ME, Dorey F, Aronson WJ. Defining the ideal cutpoint for determining PSA recurrence after radical prostatectomy. Urology. 2003;61(2):365-369. 15. Han M, Partin AW, Zahurak M, Piantadosi S, Epstein JI, Walsh PC. Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer. J Urol. 2003;169(2):517-523. 16. Chen CD, Welsbie DS, Tran C, et al. Molecular determinants of resistance to antiandrogen therapy. Nat Med. 2004;10(1):33-39. 17. Holzbeierlein J, Lal P, LaTulippe E, et al. Gene expression analysis of human prostate carcinoma during hormonal therapy identifies androgen-responsive genes and mechanisms of therapy resistance. Am J Pathol. 2004;164(1):217-227. 18. Attard G, Swennenhuis JF, Olmos D, et al. Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer. Cancer Res. 2009;69(7):2912-2918. 19. Taplin ME, Bubley GJ, Shuster TD, et al. Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N Engl J Med. 1995;332(21):1393-1398. 20. Linja MJ, Savinainen KJ, Saramäki OR, Tammela TLJ, Vessella RL, Visakorpi T. Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer. Cancer Res. 2001;61(9):3550-3555. 21. Tran C, Ouk S, Clegg NJ, et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 2009;324(5928):787-790. 22. Bubendorf L, Kononen J, Koivisto P, et al. Survey of gene amplifications during prostate cancer progression by high-throughput fluorescence in situ hybridization on tissue microarrays. Cancer Res. 1999;59(4):803-806. Erratum in: Cancer Res. 1999;59(6):1388. 23. Koivisto P, Kononen J, Palmberg C, et al. Androgen receptor gene amplification: a possible molecular mechanism for androgen deprivation therapy failure in prostate cancer. Cancer Res. 1997;57(2):314-319. 24. Richards J, Lim AC, Hay CW, et al. Interactions of abiraterone, eplerenone, and prednisolone with wild-type and mutant androgen receptor: a rationale for increasing abiraterone exposure or combining with MDV3100. Cancer Res. 2012;72(9):2176-2182. 25. Zhao XY, Malloy PJ, Krishnan AV, et al. Glucocorticoids can promote androgen-independent growth of prostate cancer cells through a mutated androgen receptor. Nat Med. 2000;6(6):703-706. Erratum in: Nat Med. 2000;6(8):939. 26. Veldscholte J, Ris-Stalpers C, Kuiper GG, et al. A mutation in the ligand binding domain of the androgen receptor of human LNCaP cells affects steroid binding characteristics and response to anti-androgens. Biochem Biophys Res Commun. 1990;173(2):534-540. 27. Libertini SJ, Tepper CG, Rodriguez V, Asmuth DM, Kung HJ, Mudryj M. Evidence for calpain-mediated androgen receptor cleavage as a mechanism for androgen independence. Cancer Res. 2007;67(19):9001-9005. 28. Hu R, Dunn TA, Wei S, et al. Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer. Cancer Res. 2009;69(1):16-22. 29. Dehm SM, Schmidt LJ, Heemers HV, Vessella RL, Tindall DJ. Splicing of a novel androgen receptor exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance. Cancer Res. 2008;68(13):5469-5477.

References: 1. Supplement to: Scher HI, Solo K, Valant J, Todd MB, Mehra M. Prevalence of prostate cancer clinical states and mortality in the United States: estimates using a dynamic progression model. PLoS One. 2015;10(10):e0139440. 2. Scher HI, Solo K, Valant J, Todd MB, Mehra M. Prevalence of prostate cancer clinical states and mortality in the United States: estimates using a dynamic progression model. PLoS One. 2015;10(10):e0139440. 3. Finianos A, Gupta K, Clark B, Simmens SJ, Aragon-Ching JB. Characterization of differences between prostate cancer patients presenting with de novo versus primary progressive metastatic disease. Clin Genitourin Cancer. 2018;16(1):85-89. 4. National Cancer Institute. Cancer stat facts: prostate cancer. Accessed July 26, 2024. https://seer.cancer.gov/statfacts/html/prost.html. 5. National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER) (07-2021). https://seer.cancer.gov/about/factsheets/SEER_Overview.pdf. Accessed 02-27-2024. 6. Kelly SP, Anderson WF, Rosenberg PS, Cook MB. Past, current, and future incidence rates and burden of metastatic prostate cancer in the United States. Eur Urol Focus. 2018;4(1):121-127. 7. Supplement to: Kelly SP, Anderson WF, Rosenberg PS, Cook MB. Past, current, and future incidence rates and burden of metastatic prostate cancer in the United States. Eur Urol Focus. 2018;4(1):121-127. 8. Chen CD, Welsbie DS, Tran C, et al. Molecular determinants of resistance to antiandrogen therapy. Nat Med. 2004;10(1):33-39. 9. Holzbeierlein J, Lal P, LaTulippe E, et al. Gene expression analysis of human prostate carcinoma during hormonal therapy identifies androgen-responsive genes and mechanisms of therapy resistance. Am J Pathol. 2004;164(1):217-227. 10. Attard G, Swennenhuis JF, Olmos D, et al. Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer. Cancer Res. 2009;69(7):2912-2918. 11. Taplin ME, Bubley GJ, Shuster TD, et al. Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N Engl J Med. 1995;332(21):1393-1398. 12. Linja MJ, Savinainen KJ, Saramäki OR, Tammela TLJ, Vessella RL, Visakorpi T. Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer. Cancer Res. 2001;61(9):3550-3555. 13. Tran C, Ouk S, Clegg NJ, et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 2009;324(5928):787-790. 14. Bubendorf L, Kononen J, Koivisto P, et al. Survey of gene amplifications during prostate cancer progression by high-throughput fluorescence in situ hybridization on tissue microarrays. Cancer Res. 1999;59(4):803-806. Erratum in: Cancer Res. 1999;59(6):1388. 15. Koivisto P, Kononen J, Palmberg C, et al. Androgen receptor gene amplification: a possible molecular mechanism for androgen deprivation therapy failure in prostate cancer. Cancer Res. 1997;57(2):314-319. 16. Richards J, Lim AC, Hay CW, et al. Interactions of abiraterone, eplerenone, and prednisolone with wild-type and mutant androgen receptor: a rationale for increasing abiraterone exposure or combining with MDV3100. Cancer Res. 2012;72(9):2176-2182. 17. Zhao XY, Malloy PJ, Krishnan AV, et al. Glucocorticoids can promote androgen-independent growth of prostate cancer cells through a mutated androgen receptor. Nat Med. 2000;6(6):703-706. Erratum in: Nat Med. 2000;6(8):939. 18. Veldscholte J, Ris-Stalpers C, Kuiper GG, et al. A mutation in the ligand binding domain of the androgen receptor of human LNCaP cells affects steroid binding characteristics and response to anti-androgens. Biochem Biophys Res Commun. 1990;173(2):534-540. 19. Libertini SJ, Tepper CG, Rodriguez V, Asmuth DM, Kung HJ, Mudryj M. Evidence for calpain-mediated androgen receptor cleavage as a mechanism for androgen independence. Cancer Res. 2007;67(19):9001-9005. 20. Hu R, Dunn TA, Wei S, et al. Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer. Cancer Res. 2009;69(1):16-22. 21. Dehm SM, Schmidt LJ, Heemers HV, Vessella RL, Tindall DJ. Splicing of a novel androgen receptor exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance. Cancer Res. 2008;68(13):5469-5477.

1-800-727-7003
AstellasAnswers.com

Indications

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

Important Safety Information

Important Safety Information and Indications

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.

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 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

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)

 

Reference: 1. XTANDI. Package insert. Northbrook, IL: Astellas Pharma US, Inc; 2025.

1-800-727-7003
AstellasAnswers.com

Indications

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

Important Safety Information

Important Safety Information and Indications

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.

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 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

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

 

Reference: 1. XTANDI. Package insert. Northbrook, IL: Astellas Pharma US, Inc; 2025.