Phase Ii Trial Of Definitive Radiotherapy With Leuprolide And Enzalutamide In High-Risk Prostate Cancer

323 Background: Adding enzalutamide to standard LHRH agonist and primary radiation therapy may improve the outcomes in patients with high-risk prostate cancer. Methods: All patients met at least 2 of the following criteria: stage cT3a/b, PSA≥20 ng/mL, Gleason Grade 8-10, ≥33% core involvement on biopsy; or had pelvic lymph node involvement ≥1cm on CT or MRI. All patients were started on 24 months of leuprolide and enzalutamide and then underwent 5 weeks of IMRT (whole pelvis, 45Gy total) followed by a brachytherapy boost. PSA, Testosterone (T) and basic labs were followed during and after treatment. Primary outcome was to assess the safety, tolerability, and feasibility of the protocol and PSA complete response (PSA-CR, defined as PSA nadir ≤0.3). Secondary outcomes included: time to biochemical recurrence (BCR) and progression free survival (PFS). Results: 16 patients were enrolled, 2 were not eligible and 3 withdrew before starting treatment. Mean age at enrollment was 68.6 years (SD 9.4). Median follow up time was 28.27 months (IQR 27.3 – 29.1 months). Median time to PSA-CR was 4.20 months (IQR 3.47 – 4.87 months). Currently all patients still have PSA-CR (Table), and none have BCR per ASTRO Phoenix criteria. All-cause, any grade adverse events (AE) were reported in all 11 (100%) patients with 4 (36.4%) experiencing grade 3 AE. One (9.09%) treatment related serious AE (seizure) occurred. There were no grade 5 AE (death related to AE). 4 subjects stopped treatment early due to: seizure, myalgias, hematuria and social reasons. Most patients however were able to complete the 24 months of leuprolide and enzalutamide: median treatment duration was 24.0 months (IQR 12.1 – 24.0 months). Conclusions: Most patients were able to tolerate and complete the entire 24 months of treatment as originally planned. Currently no patients have met criteria for PSA recurrence. Will plan to follow up patients until month 36 to help determine true BCR rates and PFS. Clinical trial information: NCT02508636. [Table: see text]