Taro Iguchi 1, Satoshi Tamada 2, Minoru Kato 2, Sayaka Yasuda 2, Yuichi Machida 3, Tetsuji Ohmachi 4, Keiichi Ishii 5, Hiroyuki Iwata 6, Shinji Yamamoto 7, Tomohiro Kanamaru 8, Kazuya Morimoto 9, Taro Hase 10, Koichiro Tashiro 11, Koji Harimoto 12, Takashi Deguchi 13, Takahisa Adachi 14, Katsuki Iwamoto 15, Yoshinori Takegaki 16, Tatsuya Nakatani
Main idea: As an alternative anti-androgen therapy in patients with castration-resistant prostate cancer who fail bicalutamide-combined androgen blockade therapy, enzalutamide provides superior clinical outcomes compared with flutamide. Enzalutamide should be preferred over flutamide in these patients.
Background: Before the androgen target therapy era, flutamide was widely used for castration-resistant prostate cancer in Japan. Enzalutamide is currently the recommended treatment; however, the efficacy and safety of enzalutamide and flutamide after combined androgen blockade therapy with bicalutamide, has not been compared.
Methods: Patients with castration-resistant prostate cancer who received combined androgen blockade therapy with bicalutamide were randomly assigned to receive either enzalutamide or flutamide. The primary endpoint for efficacy was the 3-month prostate-specific antigen response rate.
Results: Overall, 103 patients were enrolled. The 3- (80.8% vs. 35.3%; p < 0.001) and 6-month (73.1% vs. 31.4%; p < 0.001) prostate-specific antigen response rates were higher in the enzalutamide than in the flutamide group. The 3-month disease progression rates (radiographic or prostate-specific antigen progression) were 6.4% and 38.8% in the enzalutamide and flutamide groups, respectively [hazard ratio (HR): 0.16; 95% confidence interval (CI): 0.05-0.47; p < 0.001]; the 6-month rates were 11.4% and 51.1%, respectively (HR 0.22; 95% CI 0.09-0.50; p < 0.001). Enzalutamide provided superior prostate-specific antigen progression-free survival compared with flutamide (HR 0.29; 95% CI 0.15-0.54; p < 0.001). Median time to prostate-specific antigen progression-free survival was not reached and was 6.6 months in the enzalutamide and flutamide groups, respectively.