Phase II trial of 6 months ADT/abiraterone acetate plus prednisone (AAP) and definitive radiotherapy (AbiRT) for men with intermediate to high risk localized prostate cancer.

Abstract

11 Background: Combined external beam radiotherapy (RT) and androgen deprivation therapy (ADT) improves survival over RT alone for high risk prostate cancer (PC). Long-term ADT use, currently recommended for high risk PC, also increases toxicity. Recent data suggests synergistic efficacy with the addition of abiraterone acetate plus prednisone (AAP) to RT/ADT. Potent androgen blockade may provide biochemical control with short-term ADT course in men with aggressive but localized PC. Methods: This was a two center prospective phase 2 single arm clinical trial within the Department of Defense PCCTC (NCT01717053). Eligibility included 2+ intermediate or 1 high NCCN risk factors and no metastatic disease. Men received 6 months of ADT concurrently with 1000mg AA/5mg P daily and 78 Gy RT to prostate/SV. Primary endpoint was PSA < 0.1 ng/ml at 1 year. Secondary objectives included BPFS, PSA nadir, testosterone recovery, toxicity, and patient-reported QOL. Results: We enrolled 37 men (82% white, 18% black) with intermediate to high risk localized PC; 33 completed course of treatment (4 patients halted early for personal preference (N = 2), planned prostatectomy, or renal artery stenosis). Median age was 66 years; 46% Gleason 8-10, 40% Gleason 4+3 = 7, 62% T1c. Median follow-up is 23 months. Regimen was well tolerated with 12 (32%) G3 toxicities (10 hypertension, 2 hyperglycemia, 1 hypokalemia); no G4-5 or unexpected toxicities were observed. At 12 months from enrollment, PSA remained at undetectable levels in 52% of men. Testosterone recovery to normal lab value occurred in 12 (62%) at 12 months. In those patients, 20 (95%) and 21 (100%) remained with PSA under 0.5 and 1.0 ng/ml, respectively. No patient has failed by Phoenix definition to date. 1 year EPIC QOL had median summary scores above 90 for incontinence, urinary, bowel, hormonal, and satisfaction. Sexual summary score fell from median of 46 at baseline to 26 at 1 year. Conclusions: In men with high risk intermediate or limited high risk PC, utilizing short-term ADT/AAP with definitive RT shows 1) high rate of testosterone recovery and good quality of life and 2) excellent PSA control at 1 and 2 years. Clinical trial information: NCT01717053.