Analysis of overall survival in patients with nonmetastatic castration-resistant prostate cancer treated with vaccine, nilutamide, and combination therapy

Purpose: We reported previously the first randomized study of any kind in patients with nonmetastatic, castrate-resistant prostate cancer. The study employed vaccine, the hormone nilutamide, and the combined therapy (crossover for each arm) with an endpoint of time to progression. We now report survival analyses at 6.5 years from the initiation of therapy with a median potential follow-up of 4.4 years. Experimental Design: Forty-two patients were randomized to receive either a poxvirus-based prostate-specific antigen (PSA) vaccine or nilutamide. Patients in either arm who developed increasing PSA without radiographic evidence of metastasis could cross over to receive the combined therapies. Results: Median survival among all patients was 4.4 years from date of enrollment. Median survival exhibited a trend toward improvement for patients initially randomized to the vaccine arm (median, 5.1 versus 3.4 years; P = 0.13). Starting from the on-study date, the retrospectively determined subset of 12 patients who initially received vaccine and then later received nilutamide suggested improved survival compared with the 8 patients who began with nilutamide and subsequently were treated with vaccine (median, 6.2 versus 3.7 years; P = 0.045). A subgroup analysis of patients randomized to the vaccine arm versus the nilutamide arm showed substantial improvements in survival if at baseline patients had a Gleason score <7 (P = 0.033) and PSA <20 ng/dL (P = 0.013) or who had prior radiation therapy (P = 0.018). Conclusions: These data indicate that patients with nonmetastatic castration-resistant prostate cancer (D0.5) who receive vaccine before second-line hormone therapy may potentially result in improved survival compared with patients who received hormone therapy and then vaccine. These data also suggest that patients with more indolent disease may derive greater clinical benefit from vaccine alone or vaccine before second-line hormone therapy compared with hormone therapy alone or hormone therapy followed by vaccine. These findings have potential implications for both the design and endpoint analysis of larger vaccine combination therapy trials.