RESUMO
Firstline chemotherapy for men with metastatic castrationresistant prostate cancer (mCRPC) has been employed to improve overall survival (OS) and progressionfree survival (PFS). However, several new agents for CRPC after firstline chemotherapy prolonged survival by only a few months. To develop a new treatment modality, we conducted a phase III randomized trial of personalized peptide vaccination (PPV) for human leukocyte antigen (HLA)A24positive patients with castrationresistant prostate cancer (CRPC) for whom docetaxel chemotherapy failed. This randomized, doubleblind, placebocontrolled, phase III trial was carried out at 68 medical centers in Japan. Patients were randomly assigned at a 2:1 ratio to receive PPV or placebo. Four of 12 warehouse peptides selected based on preexisting peptidespecific immunoglobulin G levels or the corresponding placebo were subcutaneously injected in 6 doses weekly and then biweekly following the maximum of 30 doses until disease progression. The primary endpoint was overall survival (OS). Efficacy analyses were performed by the full analysis set. 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), 1318.2] with PPV and 16.9 months (95% CI, 13.120.4) with placebo [hazard ratio (HR), 1.04, 95% CI, 0.801.37; P=0.77]. Grade ≥3 adverse events were observed in 41% of 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, 0.330.93; P=0.03) or ≥26% lymphocytes (HR, 0.70, 95% CI, 0.520.92; P=0.02) at baseline. PPV did not prolong OS in HLAA24positive 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 baseline can receive survival benefits from PPV treatment.
