Enzalutamide (XTANDI™) 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) according to new results from the AFFIRM study published in Lancet Oncology.1

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

Professor Johann De Bono, 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 is a novel, once-daily, oral androgen receptor signalling inhibitor for the treatment of 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 first 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).
  • Enzalutamide significantly 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 significantly 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

About AFFIRM2,6

The phase III AFFIRM trial is a randomised, double-blind, placebo-controlled, multinational 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. Enrolment 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.

The AFFIRM 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 (rPFS) and time to first skeletal-related event (SRE).

In the phase III AFFIRM 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.


XTANDI (enzalutamide) is a novel, oral, once-daily androgen receptor signalling inhibitor which works in three distinct ways: it inhibits testosterone binding to androgen receptors, nuclear translocation of androgen receptors; and DNA binding and activation by androgen receptors. Xtandi is currently licensed in Europe for the treatment of adult men with mCRPC whose disease has progressed on or after docetaxel therapy. Marketing authorisation was granted by the European Commission on June 21, 2013.