Attard G, Murphy L, Clarke NW, et al. - In high-risk non-metastatic prostate cancer cases, significantly higher rates of metastasis-free survival were achieved with combination therapy vs androgen-deprivation therapy (ADT) alone. Abiraterone acetate with prednisolone deserves to be considered a new standard treatment for this population.

• Researchers studied new data from two randomized controlled phase 3 trials conducted in a multiarm, multistage platform protocol to examine the efficacy of adding abiraterone and prednisolone alone or with enzalutamide to ADT in men with high-risk non-metastatic prostate cancer.

• Both trials involved randomization of patients (1:1) to ADT alone (control group), or with oral abiraterone acetate (1,000 mg daily) and oral prednisolone (5 mg daily; combination-therapy group).

• Enzalutamide (160 mg daily orally) was also given to the combination-therapy group in the second trial with no overlapping controls.

• The combination-therapy groups exhibited significantly longer metastasis-free survival vs the control groups (hazard ratio [HR] 0·53, 95% CI 0·44–0·64); and 6-year metastasis-free survival was 82% (95% CI 79–85) vs 69% (66–72) in the combination-therapy group and control group, respectively.

• Metastasis-free survival did not differ when enzalutamide and abiraterone acetate were given concurrently vs abiraterone acetate alone (interaction HR 1·02, 0·70–1·50).

• The combination-therapy groups had significantly longer overall survival (HR 0·60, 95% CI 0·48–0·73), prostate cancer-specific survival (0·49, 0·37–0·65), biochemical failure-free-survival (0·39, 0·33–0·47), and progression-free-survival (0·44, 0·36–0·54), vs the control groups.

• During the first 24 months, adverse events grade 3 or higher occurred in 37% and 29% of the patients in the combination-therapy and control groups of the abiraterone trial, respectively, and in 58% and 32% in the combination-therapy and control groups of the abiraterone and enzalutamide trial, respectively.