Background: Sipuleucel-T is an investigational, active cellular immunotherapy product for prostate cancer. To explore the potential for benefit in ADPC, sipuleucel-T was studied in a randomized, double blind, multi-center, placebo-controlled study, P-11.
Methods: Men with ADPC were randomized (2:1) to sipuleucel-T or placebo, administered in weeks 0, 2, and 4, following 3-months of hormonal therapy. Eligible patients had a rise in serum prostate specific antigen (PSA) as the only sign of disease recurrence after prostatectomy. PSA kinetics were evaluated by time to biochemical failure (BF), defined as any PSA ≥ 3 ng/mL (primary endpoint), as well as PSA doubling time (PSADT). Clinical endpoints included time to distant metastases (DF) and survival. The effect of a single booster infusion of sipuleucel-T on the immune system was also evaluated.
Results: 176 patients were randomized (117 sipuleucel-T:59 placebo) and analyzed by intent to treat. Median time to BF was 18.0 months for sipuleucel-T and 15.4 months for placebo (hazard ratio (HR)=0.94 [95% confidence interval (CI): 0.64, 1.38]; p>0.05, log rank). The hazard ratio for BF was 0.80 in favor of sipuleucal-T ([95%CI: 0.53, 1.20], p>0.05) when the analysis was restricted to patients with a confirmed BF. An analysis of PSADT calculated from 90 days following randomization to BF or the initiation of systemic therapy demonstrated that patients randomized to sipuleucel-T had a 35% increase in PSADT (125 vs 91 days; p=0.046, F-test). PSADT calculated after patient testosterone recovery to baseline levels demonstrated a 48% increase in PSADT for the sipuleucel-T arm (155 vs 105 days; p=0.038). Only 16% of patients developed distant metastases. The hazard ratio for time to DF was 0.78 (95%CI: 0.34, 1.58, p=0.42, log rank). Patients are still being followed for DF and survival. The most common treatment-associated adverse events were chills, fatigue, headache, and pyrexia, which were primarily Grade 1-2.
Conclusions: Time to BF was not different between the two study arms. The differences in PSA kinetics, particularly the delay in PSADT for patients randomized to sipuleucel-T, are suggestive of the biologic activity of sipuleucel-T in men with ADPC. Additional follow-up for clinical endpoints of DF and survival is of interest.