alexa Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma.
Oncology

Oncology

Journal of Brain Tumors & Neurooncology

Author(s): Sampson JH, Heimberger AB, Archer GE, Aldape KD, Friedman AH,

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Abstract PURPOSE: Immunologic targeting of tumor-specific gene mutations may allow precise eradication of neoplastic cells without toxicity. Epidermal growth factor receptor variant III (EGFRvIII) is a constitutively activated and immunogenic mutation not expressed in normal tissues but widely expressed in glioblastoma multiforme (GBM) and other neoplasms. PATIENTS AND METHODS: A phase II, multicenter trial was undertaken to assess the immunogenicity of an EGFRvIII-targeted peptide vaccine and to estimate the progression-free survival (PFS) and overall survival (OS) of vaccinated patients with newly diagnosed EGFRvIII-expressing GBM with minimal residual disease. Intradermal vaccinations were given until toxicity or tumor progression was observed. Sample size was calculated to differentiate between PFS rates of 20\% and 40\% 6 months after vaccination. RESULTS: There were no symptomatic autoimmune reactions. The 6-month PFS rate after vaccination was 67\% (95\% CI, 40\% to 83\%) and after diagnosis was 94\% (95\% CI, 67\% to 99\%; n = 18). The median OS was 26.0 months (95\% CI, 21.0 to 47.7 months). After adjustment for age and Karnofsky performance status, the OS of vaccinated patients was greater than that observed in a control group matched for eligibility criteria, prognostic factors, and temozolomide treatment (hazard ratio, 5.3; P = .0013; n = 17). The development of specific antibody (P = .025) or delayed-type hypersensitivity (P = .03) responses to EGFRvIII had a significant effect on OS. At recurrence, 82\% (95\% CI, 48\% to 97\%) of patients had lost EGFRvIII expression (P < .001). CONCLUSION: EGFRvIII-targeted vaccination in patients with GBM warrants investigation in a phase III, randomized trial.
This article was published in J Clin Oncol and referenced in Journal of Brain Tumors & Neurooncology

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