Neoadjuvant randomized trial of degarelix (Deg) ± cyclophosphamide/GVAX (Cy/GVAX) in men with high-risk prostate cancer (PCa) undergoing radical prostatectomy (RP).

Abstract

5077 Background: GVAX-Prostate is a GM-CSF–secreting allogeneic cellular vaccine, whose immunogenicity may be enhanced by androgen ablation as well as low-dose Cy. We conducted a neoadjuvant immunologic study comparing Deg vs. Cy/GVAX→Deg. Methods: Men with high-risk PCa (T1c–3b N0 M0, Gleason 7–10) were randomized 1:1 to Deg(240 mg SQ) vs. Cy(200 mg/m2 IV)/GVAX(2.5×108 PC3 cells, 1.6×108 LNCaP cells) given 2 wk before Deg; all pts then had RP 2 wk after Deg. CD8+ T cell and Treg densities in the primary tumor were quantified by IHC (cells/mm2). Clinical endpoints were time-to-PSA-relapse, time-to-next-therapy, and time-to-metastasis. The study was powered (α = 0.05, β = 0.18) to show a 2-fold increase in mean CD8+ density with Cy/GVAX→Deg (Arm B) vs. Deg (Arm A). Results: 28 men were enrolled (Arm A = 15, Arm B = 13). A concurrent control group (N = 20) who did not receive neoadjuvant therapy provided untreated RP tumor samples. Baseline variables were balanced across study arms: 64% had Gleason ≥8, 56% were pT3b, 18% were pN1. There were nonsignificant increases in CD8+ and Treg densities in Arm B vs. A, and statistically significant increases in CD8+ and Treg densities in both arms (A, B) compared to group C (TABLE). CD8+ and Treg densities were strongly correlated. Outcomes were numerically better in Arm B vs A with respect to time-to-PSA-relapse (HR 0.42, 95%CI 0.13–1.38, P= 0.15) and time-to-next-therapy (HR 0.43, 95%CI 0.13–1.39, P= 0.16), although not statistically significant. Conclusions: Intratumoral immune infiltrates were marginally augmented by Cy/GVAX→Deg vs. Deg alone, while CD8+ and Treg densities were significantly greater in both study arms vs. control, supporting the immunogenic effects of androgen ablation. CD8+ / Treg ratios were remarkably consistent across groups. Clinical trial information: NCT01696877. [Table: see text]