A randomized phase I / II study of vascular endothelial growth factor receptor peptide vaccines for patients with hepatocellular carcinoma

Aim

We evaluated the safety and efficacy of vascular endothelial growth factor receptor (VEGFR) ‐targeted peptide vaccines for the immunization of patients with unresectable hepatocellular carcinoma who had responded to transarterial chemoembolization.

Methods

Twenty‐two patients were randomized 1:1 to receive VEGFR‐targeted peptides or placebo. The primary endpoint was the safety assessment of the immunization. The secondary endpoints were evaluation of immunological responses and clinical outcomes.

Results

The study agents induced no severe adverse event. Among the 12 patients in the vaccine group, a VEGFR1 specific cytotoxic T lymphocyte (CTL) response was induced in eight (66.7%) patients and a VEGFR2 specific CTL response was induced in ten (83.3%). The median progression free survival (PFS) and overall survival (OS) rates were 4.8 months and 52.0 months in the vaccine group, and 2.7 months and 21.8 months in the placebo group. No statistically significant differences were found between the two groups (PFS P=0.925, OS P=0.190). When divided into two groups according to immunoreactivity, the median PFS of patients with and without a strong immune response to VEGFR1 were 7.4 months and 2.7 months, and that to VEGFR2 were 10.6 months and 2.7 months, respectively; there were significant differences according to the immune response.

Conclusions

Immunotherapy with peptides vaccines targeting VEGFR1 and VEGFR2 was well tolerated with no serious adverse events. It also effectively induced peptide‐specific CTLs in patients with unresectable hepatocellular carcinoma.

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