Phase II Study of Personalized Peptide Vaccination for Previously Treated Advanced Colorectal Cancer
Mené au Japon sur 60 patients atteints d'un cancer colorectal avancé, cet essai de phase II évalue l'efficacité, du point de vue de la survie globale, et la toxicité d'un vaccin peptidique personnalisé
Since the prognosis of advanced colorectal cancer (aCRC) remains poor, development of new therapeutic approaches, including immunotherapy, would be highly desirable. In the current study, we conducted a phase II study of personalized peptide vaccination (PPV) in 60 previously treated aCRC patients, who had failed at least one regimen of standard chemo- and/or targeted therapies. For PPV, a maximum of four HLA-matched peptides were individually selected from a pool of 31 different peptide candidates based on the pre-existing host immunity, and administered subcutaneously without severe adverse events. Boosting of IgG and cytotoxic T lymphocyte (CTL) responses specific to the administered peptides was observed in 49% and 63%, respectively, of the patients, who completed the first cycles of six vaccinations. Median overall survival (OS) time was 498 days with one- and two-year survival rates of 53% and 22%, respectively. Multivariate Cox regression analysis of pre-vaccination factors showed that plasma IL-6, IP-10, and BAFF levels were significantly prognostic for OS [hazard ratio (HR) =1.508, P = 0.043; HR = 1.579, P = 0.024; HR = 0.509, P = 0.002; respectively]. In addition, increased peptide-specific CTL responses after vaccination were significantly predictive of favorable OS (HR = 0.231, P = 0.021), suggesting a causal relationship between biological and clinical efficacy of PPV. Because of the safety profile and possible clinical efficacy, next step of clinical trials of PPV would be warranted for previously treated aCRC patients.