Phase II Trial of Enzalutamide and Androgen Deprivation Therapy with Salvage Radiation in Men with High-risk Prostate-specific Antigen Recurrent Prostate Cancer: The STREAM Trial

Abstract

Background: Salvage external beam radiotherapy (RT) with androgen deprivation therapy (ADT) improves survival over RT in men with prostate cancer (PC) and rising prostate-specific antigen (PSA) levels after radical prostatectomy (RP). Objective: To investigate the safety and efficacy of enzalutamide concurrent with salvage RT and ADT. Design, setting, and participants: This was a three-center prospective phase 2 single-arm trial (NCT02057939) of men with Gleason 7-10 PC and PSA recurrence within 4 yr of RP ranging from 0.2 to 4.0 ng/dl, no prior hormonal therapy, and no radiographic evidence of metastases. We enrolled 38 men; 37 completed therapy and were evaluable with testosterone recovery at 2 yr. Intervention: Six months of ADT with 160 mg/d enzalutamide and 66 Gy RT to the prostate bed. Outcome measurements and statistical analysis: The primary endpoint was improved 2-yr progression-free survival (PFS) over historical controls. Secondary objectives included 3-yr PFS, safety, and patient-reported quality of life (QOL). Results and limitations: The primary endpoint of 2-yr PFS was 65% (95% confidence interval [CI]: 47, 78) versus 51% (95% CI: 33, 67) in a trial of men with similar eligibility treated with salvage RT and adjuvant docetaxel. The 3-yr PFS was 53%.

Adjuvant or Salvage Radiation Therapy for Prostate Cancer after Prostatectomy: Current Status, Controversies and Perspectives

“…The phase 2 STREAM study was the first to investigate the combination of enzalutamide concurrently with RT and ADT. The 2-year PFS was 65% and a 29% toxicity grade 3 rate was reported [ 53 ]. The French randomized phase 3 CARLHA-2/GETUG-AFU 33 trial (NCT04181203) comparing prostate bed and pelvic RT with 6 months of ADT ± apalutamide for high-risk relapsing patients is currently recruiting.…”

Addition of Enzalutamide to Leuprolide and Definitive Radiation Therapy Is Tolerable and Effective in High-Risk Localized or Regional Nonmetastatic Prostate Cancer: Results From a Phase 2 Trial

“…For example, Kaplan et al demonstrated effectiveness of enzalutamide monotherapy as a possible replacement for ADT in patients with intermediate PCa undergoing radiation therapy, using PSA response as a primary endpoint (31). Similarly, the STREAM and RTOG 3506 trials are currently evaluating enzalutamide in the salvage radiation setting in conjunction with ADT (26,32). Most recently, Attard et al in the phase III STAMPEDE trial show convincing evidence that addition of abiraterone with or without enzalutamide leads to improvement in metastasis-free and overall survival compared to ADT alone in high-risk PCa; although the addition of enzalutamide to abiraterone and ADT did not appear to provide additional treatment effect, the authors add the caveat that the study design could not exclude benefit of enzalutamide (33).…”

Drug Intensification in Future Postoperative Radiotherapy Practice in Biochemically-Relapsing Prostate Cancer Patients

“…Phase 2 results are pending. Enzalutamide was also evaluated in combination with salvage prostate bed radiotherapy (40). Grade 3 toxicities, mostly fatigue and hypertension, were observed in 29% of patients.…”