Phase Ii Trial Enzalutamide And Androgen Deprivation Therapy (Adt) With Salvage Radiation In Men With High Risk Psa Recurrent Prostate Cancer (Pc): The Stream Trial.

29 Background: Salvage external beam radiotherapy (RT) and hormonal therapy improves survival over RT alone in men with non-metastatic hormone naïve PC and PSA recurrence after radical prostatectomy (RP). We investigated the safety/efficacy of enzalutamide with salvage RT and ADT in this setting. Methods: This was a 3 center prospective phase 2 single arm clinical trial in the Dept of Defense Prostate Cancer Clinical Trials Consortium. Eligibility: Gleason 7-10 PC and PSA recurrence within 4 years (yrs) of RP, PSA 0.2-4.0, no prior hormonal therapy, and no metastases on CT/Bone Scan imaging. Men received 6 months (mos) of ADT with 160 mg/d enzalutamide and 66 Gy RT to the prostate bed. Primary endpoint was 2 yr PFS with testosterone (T) recovery to >100 ng/dl. Secondary objectives included PSA nadir, 3 yr PFS, safety and patient reported quality-of-life over time. This trial was designed with 84% power to detect a 20% improvement in 2 yr PFS vs historic data and a 1-sided alpha of 0.05. Results: We enrolled 38 men (90% white, 8% black, 2% Asian); 37 (97%) completed therapy and were evaluable with T recovery at 2 yrs. Median age was 64 yrs; 47% Gleason 8-10, 79% T3/T4 disease, 21% had resected N+ PC; median PSA was 0.4 (0.19-4.19). Median follow-up is 29.5 mo. Treatment was well tolerated with 11 patients (29%) experiencing G3 toxicities (including 4 HTN, 2 urinary retention, 2 CV events); no G4-5 or unexpected toxicities were observed. T recovery occurred in 35 (95%) at 12 mos. The primary endpoint of 2 yr PFS was 65% (95% CI: 47%-78% vs. historic controls with 51% 2 yr PFS rate) among the 37 patients with T recovery. PSA remained at undetectable levels in 69% at 2 yrs. The 3 yr PFS was 53% (95% CI: 36%, 68%). QOL data over time suggest short term reductions in urinary and sexual function with recovery by 12-24 mo in most men. Conclusions: Salvage enzalutamide and ADT for 6 months with RT following RP for men with PSA recurrent high risk PC is safe, and demonstrates encouraging efficacy at 2 and 3 years. Most men have testosterone recovery at 1 year. These data warrant prospective controlled phase 3 trials to assess the impact of potent AR inhibition in this curative intent setting. Clinical trial information: NCT02057939.