A Phase 2 Randomized Controlled Trial of Personalized Peptide Vaccine Immunotherapy with Low-dose Dexamethasone Versus Dexamethasone Alone in Chemotherapy-naive Castration-resistant Prostate Cancer

Background: It is well known that the prognosis of castration-resistant prostate cancer (CRPC) is poor, and several immunotherapeutic strategies have been applied to the clinical trials. Research on immunotherapy has been of special interest for the treatment of CRPC for years. Objective: To evaluate the safety of personalized peptide vaccine (PPV) immunotherapy and its clinical outcomes. Design, setting, and participants: A phase 2 randomized controlled trial of PPV immunotherapy with low-dose dexamethasone versus dexamethasone alone for chemotherapy-naive CRPC began in 2008. Eligible patients (prostate-specific antigen [PSA] < 10 ng/ml) were human leukocyte antigen (HLA) A02, A24, or A03 superfamily positive and had asymptomatic or minimally symptomatic CRPC. Patients were allocated (1: 1) to PPV plus dexamethasone (1 mg/d) or to dexamethasone (1 mg/d) alone. A maximum of four HLA-matched peptides (each 3 mg) was selected based on the preexisting immunoglobulin G responses against the 24 warehouse peptides and administered every 2 wk. Outcome measurements and statistical analysis: PSA, progression-free survival (PFS), time to initiation of chemotherapy, and overall survival (OS) were analyzed using the Kaplan-Meier method, a log-rank test, and proportional hazard analysis. Results and limitations: Overall, 37 patients received peptide vaccinations and 35 received dexamethasone alone. The primary end point was PSA PFS, which was significantly longer in the vaccination group than in the dexamethasone group (22.0 vs 7.0 mo; p = 0.0076). Median OS was also significantly longer in the vaccination group (73.9 vs 34.9 mo; p = 0.00084). The relatively small number of patients enrolled is the major limitation of the study. Conclusions: PPV immunotherapy was well tolerated and associated with longer PSA PFS and OS in men with chemotherapy-naive CRPC. A larger phase 3 study is needed to confirm our findings. Patient summary: We compared clinical outcomes of the treatment with personalized peptide vaccine plus dexamethasone versus dexamethasone alone. Our data provide promising evidence of clinical benefit for peptide vaccines. Trial registration: UMIN-CTR: 000000959. (C) 2016 European Association of Urology. Published by Elsevier B.V.