Enzalutamide (Xtandi?; Astellas Pharma Inc/Medivation, Inc; The drug was formerly known as MDV3100), a novel, oral, once-daily androgen receptor signaling inhibitor, reduces the risk of skeletal-related events compared with placebo, as well as reducing pain and increasing quality of life in men with metastatic castration-resistant prostate cancer (mCRPC). This conclusion is based on new results from the AFFIRM study published in The Lancet Oncology.[1][3]

Bone is the most common site of spread in prostate cancer, accounting for about 90% of metastases, resulting in some of the most painful and functionally compromising complications of the disease.[1]


…health related quality of life data (HRQoL) endorses the fact that enzalutamide is a major advance in the treatment of prostate cancer…


Trial design
The AFFIRM trial is a randomised, double-blind, placebo-controlled, multinational phase III trial evaluating enzalutamide (160 mg/day) versus placebo in 1,199 men with progressive metastatic castration-resistant prostate cancer who were previously treated with docetaxel- based chemotherapy. Enrollment was completed in November 2010 and the interim analysis was triggered at 520 events. The median age of study participants was 69 years at baseline.[2][6][7]

The study was conducted at sites in the United States, Canada, Europe, Australia, South America and South Africa. The primary endpoint of the AFFIRM trial was overall survival. Key secondary endpoints included time to Prostate-Specific Antigen(PSA) progression, radiographic Progression Free Survival orrPFS and time to first Skeletal-Related Eventor SRE.

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Trial related adverse events
In the trial, enzalutamide was generally well tolerated. The most common adverse reactions were hot flushes and headache. Seizure was reported in 0.8% of enzalutamide-treated patients. Serious adverse events, adverse events causing patients to stop treatment, and adverse events causing death were all lower in the enzalutamide group than in the placebo group.

Health Related Quality of Life
Professor Johann De Bono, MD, PhD, MSc, FRCP., Professor of Experimental Cancer Medicine at The Institute of Cancer Research London, and Head of the Drug Development Unit at The Royal Marsden NHS Foundation Trust, comments: “These quality of life data endorse the fact that enzalutamide is a major advance in the treatment of prostate cancer.”

Enzalutamide, targets multiple steps in the androgen-receptor?signaling pathway, the major driver of prostate-cancer growth. The drug inhibits testosterone binding to androgen receptors, nuclear translocation of androgen receptors, and DNA binding and activation by androgen receptors. Enzalutamide is used to treat men with mCRPC whose disease has progressed on or after docetaxel therapy. [3] Prospective analyses of secondary endpoints in the Phase III AFFIRM trial examined first skeletal-related events and investigated several measures of pain control and patient-reported health related quality of life (HRQoL).[1]

Researchers found that:[1]

  • enzalutamide reduced the risk of skeletal-related events (such as radiation treatment to the bone and spinal cord compression) by 31% versus placebo (p=0.0001). The time to ?rst skeletal-related event was significantly longer for patients on enzalutamide compared to placebo (16?7 months vs. 13?3 months; hazard ratio 0?69; p=0?0001).
  • the drug signi?cantly improved both pain severity and interference from baseline to week 13 compared with placebo (p<0?0001), as well as reducing the risk of pain progression (p=0.0018).
  • Compared to the placebo group, a signi?cantly higher percentage of patients on enzalutamide reported improvements in quality of life measured by FACT-P, a questionnaire used in prostate cancer studies which includes physical, emotional and functional wellbeing. Patients in the enzalutamide group had a significantly longer time to HRQoL deterioration than those in the placebo group (9?0 months vs. 3?7 months; HR 0?45; p<0?0001).

Prostate cancer is the most common cancer in men in Europe, accounting for over 20% of all cancer diagnoses (excluding non-melanoma skin cancer) and is the third most common cause of cancer death in Europe.[4] Up to 40% of men with prostate cancer develop metastatic disease and a high number of these men eventually fail androgen deprivation treatment, which is called Castration-Resistant Prostate Cancer (CRPC).[5]

For more information:
[1]Fizazi K, Scher HI, Miller K, Basch E, Sternberg CN, Cella D, Forer D, Hirmand M, de Bono JS. Effect of enzalutamide on time to first skeletal-related event, pain, and quality of life in men with castration-resistant prostate cancer: results from the randomised, phase 3 AFFIRM trial. Lancet Oncol. 2014 Sep;15(10):1147-56. doi: 10.1016/S1470-2045(14)70303-1. Epub 2014 Aug 4.[Article][PubMed]
[2] Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND, Armstrong AJ, Flaig TW, Fl?chon A, Mainwaring P, Fleming M, Hainsworth JD, Hirmand M, Selby B, Seely L, de Bono JS. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012 Sep 27;367(13):1187-97. Epub 2012 Aug 15. [Article][PubMed]
[3] European Medicines Agency, XTANDI, (enzalutamide) Summary of Product Characteristics, 2013. Last Accessed: September 5, 2014 [SPC]
[4]Ferlay J, Shin HR, Bray F et al. Globocan 2008 v2.0, cancer incidence and mortality worldwide. IARC CancerBase No. 10. Lyon, France: International Agency for Research on Cancer 2010. Last accessed September 5, 2014 [Internet]
[5] Beltran H, Beer TM, Carducci MA, de Bono J, Gleave M, Hussain M, Kelly WK, Saad F, Sternberg C, Tagawa ST, Tannock IF. New therapies for castration-resistant prostate cancer: efficacy and safety. Eur Urol. 2011 Aug;60(2):279-90. doi: 10.1016/j.eururo.2011.04.038. Epub 2011 May 4.[Article][PubMed]
[6] Scher HI. 2012 Genitourinary Cancers Symposieptor signaling inhibitor (ARSI), on overall survival in patients with prostate cancer postdocetaxel: Results from the phase III AFFIRM study. 2012 Genitourinary Cancers Symposium (General Session II: Castration-Resistant Prostate Cancer — Treatment Sequencing and Implementation; Prostate Cancer Track. J Clin Oncol 30, 2012 (suppl 5; abstr LBA1)[Abstract]

Clinical trials
[7] Safety and Efficacy Study of MDV3100 in Patients With Castration-Resistant Prostate Cancer Who Have Been Previously Treated With Docetaxel-based Chemotherapy (AFFIRM) – NCT00974311 [Study Record Detail]

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