Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Peptide Vaccine for Prevention of Recurrent Colorectal Adenoma

Abstract

AbstractObjectiveVaccines against antigens expressed on adenomas could prevent new adenoma formation. We assessed whether a MUC1 peptide vaccine produces an immune response and prevents subsequent colonic adenoma formation.DesignMulticenter, double blind, placebo-controlled randomized trial in individuals age 40-70 with diagnosis of an advanced adenoma ≤1 year from randomization. Vaccine was administered at 0, 2, and 10 weeks with a booster injection at week 53. Adenoma recurrence was assessed ≥1 year from randomization. The primary endpoint was vaccine immunogenicity at 12 weeks defined by anti-MUC1 ratio ≥2.0.Results53 participants received the MUC1 vaccine and 50 placebo. 13/52 (25%) of MUC1 vaccine recipients had a ≥2-fold increase in MUC1 IgG (range 2.9-17.3) at week 12 vs. 0/50 placebo recipients (1-sided Fisher’s exact P<0.0001). Of the 13 responders at week 12, 11 (84.6%) had a ≥2-fold increase in MUC1 IgG with the booster and were considered immune responders. A recurrent adenoma was observed in 31 of 47 (66.0%) in the placebo group vs. 27 of 48 (56.3%) participants in the MUC1 group (adjusted relative risk (aRR) = 0.83 [95% CI, 0.60-1.14], P=0.25). Adenoma recurrence occurred in 3/11 (27.3%) immune responders, (aRR = 0.41 [95% CI, 0.15-1.11], P=0.08). Vaccine recipients had more injection site reactions than placebo recipients, but there was no difference in serious adverse events.ConclusionAn immune response was observed only in vaccine recipients. Overall adenoma recurrence was not different than placebo, but a 38% absolute reduction in adenoma recurrence was observed in immune responders.ClinicalTrials.gov Identifier: NCT02134925.https://clinicaltrials.gov/ct2/show/NCT02134925Key PointsWhat is already knownAntigens expressed on colonic adenomas are potential targets for immunopreventive vaccines. An effective vaccine could prevent subsequent adenoma formation.What this Study AddsIn this multicenter, double blind, placebo-controlled randomized trial, MUC1 vaccine recipients developed an immune response. Overall adenoma recurrence was not different than placebo, but a 38% absolute reduction in adenoma recurrence was observed in immune responders.How this study might affect research, practice or policyVaccine immunoprevention is a potential new frontier to colorectal cancer prevention.