Xtandi (enzalutamide) for prostate cancer is showing favourable results in clinical trials, increasing progression-free survival and overall survival.
Prostate cancer is the most commonly diagnosed cancer in men worldwide. The basis of current hormonal therapies for prostate cancer is to deprive the cancer cells of the hormone androgen by inhibiting the activity of its cellular receptor the androgen receptor.
Xtandi (enzalutamide), previously known as MDV3100, produced by Medivation, is an anti-androgen drug that was designed to inhibit androgen receptor signaling by binding to the receptor in place of androgen. Studies have demonstrated that Xtandi binds to the androgen receptor with five times greater affinity than bicalutamide, another anti-androgen drug currently used to treat prostate cancer.
A previous phase 3 study of Xtandi demonstrated an increase in overall survival, and survival without progression, in men who had prostate cancer that was resistant to prior androgen deprivation therapy, and who had previously also had chemotherapy. In addition, a phase 1-2 trial demonstrated promising results in men with prostate cancer that was resistant to hormonal therapy, who had not yet undergone any chemotherapy.
A recent phase 3 clinical trial was designed to test the effectiveness of Xtandi in men with metastatic prostate cancer that had progressed despite androgen deprivation therapy, but who had not yet had any chemotherapy. The study was an international, double blind, randomised, placebo-controlled, phase 3 trial of Xtandi for prostate cancer. The trial took place between September 2010 and September 2012 across 207 centres worldwide. The participants consisted of 1717 patients who were randomly assigned to either an Xtandi treatment group (160mg daily dose) (872 patients), or placebo group (845 patients). The patients were assessed by either computed tomography or MRI at time points 0, 9, 17, and 25 weeks, and every 12 weeks after that. The primary endpoints were progression-free survival and overall survival.
Progression-free survival was greater in the Xtandi treatment group (65%) compared to the placebo group (14%) at the 12 month time-point. Xtandi treatment was associated with a 29% reduction in risk of death, with a median overall survival of 32.4 months, compared to 30.2 months in the placebo group. Patients in the Xtandi treatment group also had an increase in time until the need for initiation of subsequent chemotherapy. Xtandi had an acceptable safety profile, with adverse events that included: fatigue, back pain, constipation, and arthralgia.
Overall, the study reported increases in both progression-free and overall survival, in addition to a delay in the beginning of chemotherapy treatment, with favourable side effect profiles.
There are approximately 40 clinical trials currently scheduled to test Xtandi for prostate cancer. These studies include those that are designed to assess the effects of Xtandi alone, or in combination with other prostate cancer therapies, at varying stages of disease progression. A comprehensive list of actively recruiting studies can be found by following the link below: http://www.clinicaltrials.gov/ct2/results?term=enzalutamide+AND+prostate+cancer&recr=Open&no_unk=Y&pg=1
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. “Global cancer statistics”. CA Cancer J Clin 2011;61:69-90
Xtandi Information Sheet. Available from: https://www.xtandihcp.com/ Last Accessed: Sept 4, 2014.
Tran, C, Ouk, S, Clegg, NJ, Chen, Y, Watson, PA, Arora, V, Wongvipat, J, Smith-Jones, PM, Yoo, D, Kwon, A, Wasielewska, T, Welsbie, D, Chen, C Higano, CS, Beer, TM, Hung, DT, Scher, HI, Jung, M, and Sawyers, CL. “Development of a Second-Generation Antiandrogen for Treatment of Advanced Prostate Cancer” Science. May 8, 2009; 324(5928): 787–790.
Beer, TM, Armstrong, AJ, Rathkopf, DE, Loriot, Y, Sternberg, CN, Higano, CS, Iversen, P, Bhattacharya, S, Carles, J, Chowdhury, S, Davis, ID, de Bono, JS, Evans, CP, Fizazi, K, Joshua, AM, Kim, CS, Kimura, G, Mainwaring, P, Mansbach, H, Miller, K, Noonberg, SB, Perabo, F, De Phung, Saad, F, Scher, HI, Taplin, ME, Venner, PM, Tombal, B. for the PREVAIL Investigators. “Enzalutamide in Metastatic Prostate Cancer before Chemotherapy” N Engl J Med 2014; 371:424-433, July 31, 2014. DOI: 10.1056/NEJMoa1405095
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Written by Deborah Tallarigo, PhD