Long-term safety and efficacy of enzalutamide for men with castration-resistant prostate cancer: a multicenter, prospective DELC study

Abstract Background Alternative antiandrogen therapy (AAT) has been widely used as a first-line treatment for castration-resistant prostate cancer (CRPC), and it may affect treatment outcome of subsequent androgen receptor axis-targeted agents. We conducted a prospective observational study to evaluate the efficacy of enzalutamide in patients with CRPC who underwent prior combined androgen blockade with bicalutamide and then AAT with flutamide. Methods This prospective observational study enrolled 163 Japanese patients with CRPC who underwent AAT with flutamide following failure of initial combined androgen blockade with bicalutamide in multiple institutions between January 2016 and March 2019. Primary endpoint was overall survival. Administration of enzalutamide was started at 160 mg orally once daily in all patients. Results Median follow-up period was 25.8 months, the rate of decline of prostate-specific antigen by 50% or more was 72.2%, and median overall survival was 42.05 months. Multivariate analysis revealed that higher pretreatment serum prostate-specific antigen (≥ 11.3 ng/mL; p = 0.004), higher neuron-specific enolase (p = 0.014), and higher serum interleukin-6 (≥ 2.15 pg/mL; p = 0.004) levels were independent risk factors for overall survival. Fatigue (30.0%), constipation (19.6%), and appetite loss (17.8%) were the most common clinically relevant adverse events. The enzalutamide dose was not reduced in any patient under the age of 70, but adherence was decreased in those over 70. Conclusions Although the enzalutamide response period appeared shorter due to prior AAT, overall survival was deemed equivalent compared to previous reports. Neuron-specific enolase and interleukin-6 levels in serum were suggested as prognostic factors with potential clinical utility.