Personalized peptide vaccination for castration-resistant prostate cancer progressing after docetaxel: A randomized, double-blind, placebo-controlled, phase III trial

Background To develop a new treatment modality, we conducted a phase 3 randomized trial of personalized peptide vaccination (PPV) for human leukocyte antigen (HLA)-A24-positive patients with castration-resistant prostate cancer (CRPC) for whom docetaxel chemotherapy failed. Methods This randomized, double-blind, placebo-controlled, phase 3 trial was done at 68 medical centers in Japan. Eligible patients were aged 20 years or older, positive immunoglobulin G (IgG) responses to at least 2 of 12 warehouse peptides, an Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of at least 12 weeks, serum testosterone level of ≤ 50 ng/dl, and satisfactory bone marrow function, hepatic function, and renal function. Patients were randomly assigned in a 2:1 ratio to receive PPV or placebo. Four of 12 warehouse peptides selected based on pre-existing peptide-specific IgG levels or the corresponding placebo were subcutaneously injected in 6 doses weekly and then bi-weekly following the maximum of 30 doses until disease progression. The primary end point was overall survival (OS). Efficacy analyses were by the full analysis set. Results Between August 2013 and April 2016, 310 patients were randomly assigned, and 306 patients were analyzed. Baseline characteristics were balanced between groups. The estimated median OS was 16.1 months (95% confidence interval [CI], 13–18.2) with PPV and 16.9 months (95% CI, 13.1–20.4) with placebo (hazard ratio [HR], 1.04, 95% CI, 0.80–1.37; p = 0.77). Grade ≥ 3 adverse events were observed in 41% in both groups. The analysis of treatment arm effects among subgroups revealed lower HRs for OS in favor of the PPV arm in patients with < 64% neutrophils (HR, 0.55, 95% CI, 0.33–0.93; p = 0.03) or ≥ 26% lymphocytes (HR, 0.70, 95% CI, 0.52–0.92; p = 0.02) at base line. Conclusions PPV did not prolong OS in HLA-A24-positive patients with CRPC progressing after docetaxel chemotherapy. Subgroup analysis suggested that the patients with a lower proportion of neutrophils or a higher proportion of lymphocytes at base line can receive survival benefits from PPV treatment.