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Xtandi™ (enzalutamide) now licensed for use in the UK to treat men with advanced prostate cancer, following initial hormone treatment failure

XTANDI TM() is now licensed in Europe and is already funded in England on the Fund,2 for the treatment of with metastatic castration-resistant (mCRPC) who are asymptomatic or mildly symptomatic after failure of in whom chemotherapy is not yet clinically indicated.1 The licence has been updated based on data from the PREVAIL study which showed that treatment with enzalutamide reduced the risk of disease progression measured using scans, or death by 81% (HR=0.19; p<0.001) versus placebo and significantly improved overall survival (reduced risk of death by 29% HR=0.71; p<0.001) during the study.3 Moreover, in men treated with enzalutamide the need for chemotherapy was delayed by 17 months compared to placebo (28.0 months versus 10.8 months, respectively; HR=0.35; p<0.001).3

Dr. Alison Birtle Honorary Clinical Senior Lecturer & Consultant Oncologist, Royal Preston Hospital said: “The approval of enzalutamide for treatment of mCRPC after initial hormone therapies have failed is a much needed development in prostate cancer. For many men with advanced prostate cancer, enzalutamide has already shown that we can improve how long men may live with this diagnosis, and ensure they have good quality of life achieving all their milestones.”

Enzalutamide is a once-daily, oral treatment administered without the need for routine product- specific monitoring.1 Steroids are not required to be taken with enzalutamide; however, they can be prescribed at the judgement of a doctor.1

Commenting on the news Sandy Tyndale-Biscoe, Honorary Chairman of Tackle said: “Today marks a great day for the thousands of men with advanced prostate cancer who could benefit from treatment with enzalutamide. Enzalutamide, which has the potential to allow men to continue living a good quality of life, is undoubtedly an important step forward for patients. It is great to have such a treatment for prostate cancer patients with advanced disease, where treatment choices are so limited.”

?Prostate cancer is the second most common cause of cancer death in men in the UK.4 Although early stage disease can often be cured, when prostate cancer spreads to other parts of the body (known as advanced or metastatic disease), the condition is incurable.5 In patients who present with advanced disease, 72% will die within 5 years of diagnosis.6

Every year approximately 45,000 people are diagnosed with any stage of prostate cancer in the UK,7 of these it is estimated that nearly 14,000 men will be living with mCRPC.8 Patients with mCRPC regarded as asymptomatic or mildly symptomatic may be suitable for treatment with enzalutamide. This equates to over 6,200 men that could be eligible to receive enzalutamide.8,9,10

Enzalutamide was approved by the European Commission in June 2013 for the treatment of adult men with mCRPC whose disease has progressed on or after docetaxel therapy.1 This additional new indication also makes enzalutamide available for men in whom chemotherapy is not yet clinically indicated.1 Enzalutamide is currently accessible in this setting for eligible men in England via the Cancer Drugs Fund.2

About metastatic prostate cancer

One man in every eight will get prostate cancer;11 it is the second most common cause of cancer death in men in the UK.4 Although early stage disease can often be cured, when prostate cancer spreads to other parts of the body (known as metastatic prostate cancer), most commonly to the bones, the disease is incurable.5 In patients who present with advanced disease, 72% will die within five years of diagnosis.6

Treatment of metastatic prostate cancer usually involves reducing testosterone either by surgical or medical methods.5 However, the cancer can become resistant to this type of therapy at which stage it is known as metastatic castration-resistant prostate cancer (mCRPC).12 When prostate cancer is so advanced, treatment can usually be given to slow the progression of the cancer, relieve symptoms and improve quality of life.13

Enzalutamide has been shown to reduce the risk of death compared to placebo and maintain quality of life in men with advanced disease.14

About enzalutamide

Enzalutamide is an, oral, once-daily androgen receptor signalling inhibitor which works in three distinct ways: it 1) blocks androgen receptors binding to testosterone; 2) inhibits translocation of the nucleus; and 3) impairs dimer binding to DNA and modulation of gene expression.15,16 Enzalutamide is licensed in Europe to treat adult men with mCRPC who are asymptomatic or mildly symptomatic and in whom chemotherapy is not yet clinically indicated. This is in addition to the original licence, for the treatment of adult men whose disease has progressed (started to grow and spread again) on or after docetaxel therapy.1


The Phase III PREVAIL trial is a randomised, double-blind, placebo-controlled, multi-national trial that enrolled more than 1,700 patients at sites in various countries including the UK. The trial enrolled patients with metastatic prostate cancer whose disease had progressed despite treatment with androgen deprivation therapy and were not yet eligible to receive chemotherapy (i.e. were chemotherapy nai?ve). The co-primary endpoints of the trial were overall survival (OS) and radiographic progression-free survival (rPFS). The trial was designed to evaluate enzalutamide at a dose of 160 mg taken orally once-daily versus placebo.


1 Xtandi (enzalutamide) Summary of Product Characteristics

2 NHS England, National Cancer Drugs Fund List,updated October 2014 , available at http://www.england.nhs.uk/wp- content/uploads/2014/10/ncdf-list-10141.pdf last accessed December 2014

3 Beer TM, et al. Enzalutamide in Metastatic Prostate Cancer before Chemotherapy. N Engl J Med 2014; DOI: 10.1056/NEJMoa1405095

4 Cancer Research UK, Prostate Cancer, available at http://publications.cancerresearchuk.org/downloads/Product/CS_KF_PROSTATE.pdf , last accessed December 2014

5 Cancer Research UK, Treatment options for prostate cancer, available at http://www.cancerresearchuk.org/cancer-help/type/prostate-cancer/treatment/types/treatment-options-for-prostate-cancer, last accessed December 2014

6 National Cancer Institute, SEER Fast Statistics, available at, http://seer.cancer.gov/csr/1975_2009_pops09/results_merged/topic_survival.pdf , last accessed December 2014

7 Globocan, Prostate: estimated incidence, all ages, available at: http://seer.cancer.gov/csr/1975_2009_pops09/results_merged/topic_survival.pdf last accessed December 2014

8 CancerMPact, Kantar Health. Last accessed January 2013

9 National Institute for Health and Care Excellence. Single Technology Appraisal (STA). Abiraterone acetat (Zytiga) for the treatment of metastatic castration resistant prostate cancer following previous cytoxic therapy – Manufacturer’s Submission

10 Autio KA, et al. J Oncol Prac 2013;9(5):223-9

11 Prostate Cancer UK, Prostate Cancer Facts and Statistics, available at http://prostatecanceruk.org/information/prostate-cancer-facts-and-figures, last accessed December 2014

12 Maluf, F,Smaletz O, Herchenhorn, D, Castration-resistant prostate cancer: systemic therapy in 2012, Clinics (SaoPaulo) 2012, 67(4): 389-94

13 Macmillan Cancer Support. Treatment for advanced prostate cancer, available at: http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Prostate/Treatmentforadvancedprostatecancer/Overview.aspx, last accessed December 2014

14 Scher H I, et al. Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy, New England Journal of Medicine, N Engl J Med 2012; 367:1187-1197

15 Tran C et al Development of a second-generation antiandrogen for treatment of advanced prostate cancer, Science 2009; 324: 787-790

16 Hu R et al Molecular processes leading to aberrant androgen receptor signaling and castration resistance in prostate cancer Expert Review of Endocrinology and Metabolism 2010;5(5): 753-76

Astellas Pharma Limited UK