Data from a new phase II trial investigating personalized peptide vaccine (PPV) therapy in patients with chemotherapy-naive castration-resistant prostate cancer (CRPC) show that men receiving the PPV had significantly longer progression-free survival (PFS) and overall survival than men in the control group.

The study, which was performed at two centres in Japan, included 73 patients who were randomized 1:1 to receive the PPV plus low-dose dexamethasone or dexamethasone only. In their PPV approach, the investigators first screened a set of 24 peptides for immune responses mediated by cytotoxic T lymphocytes using patient serum that had been collected before vaccination. For each patient, they then selected up to four reactive peptides to be used for immunization.

Although differences in >50% decline in PSA levels at week 12 were not statistically significant, median PFS significantly differed between the PPV group and the control group (22 months versus 7 months, respectively; P = 0.0076; progression defined as two consecutive increases of 25% in PSA levels ≥2 weeks apart). In addition, estimated median overall survival was around 39 months longer in the PPV group than in the control group (P = 0.00084). “We think that the statistical difference in overall survival is the most important finding,” senior author Hirotsugu Uemura told Nature Reviews Urology. “Few previous studies of immunotherapy in patients with CRPC have indicated marked improvements in overall survival; our finding might be due to enrolment of early-stage patients in our study.”

The PPV immunotherapy was well tolerated, with no toxicities of grade ≥3 observed, and the team are now planning to perform a phase III trial in a larger cohort of patients. “We are also interested in a nonpersonalized approach using a vaccine containing multiple peptides, because the use of a fixed multipeptide mixture might be more feasible with an easier patient screening system,” Uemura concludes.