Immunologic Escape After Prolonged Progression-Free Survival With Epidermal Growth Factor Receptor Variant III Peptide Vaccination in Patients With Newly Diagnosed Glioblastoma

DOI Web Site 被引用文献17件
  • John H. Sampson
    From the Duke University Medical Center, Durham, NC; and the University of Texas M. D. Anderson Cancer Center, Houston, TX.
  • Amy B. Heimberger
    From the Duke University Medical Center, Durham, NC; and the University of Texas M. D. Anderson Cancer Center, Houston, TX.
  • Gary E. Archer
    From the Duke University Medical Center, Durham, NC; and the University of Texas M. D. Anderson Cancer Center, Houston, TX.
  • Kenneth D. Aldape
    From the Duke University Medical Center, Durham, NC; and the University of Texas M. D. Anderson Cancer Center, Houston, TX.
  • Allan H. Friedman
    From the Duke University Medical Center, Durham, NC; and the University of Texas M. D. Anderson Cancer Center, Houston, TX.
  • Henry S. Friedman
    From the Duke University Medical Center, Durham, NC; and the University of Texas M. D. Anderson Cancer Center, Houston, TX.
  • Mark R. Gilbert
    From the Duke University Medical Center, Durham, NC; and the University of Texas M. D. Anderson Cancer Center, Houston, TX.
  • James E. Herndon
    From the Duke University Medical Center, Durham, NC; and the University of Texas M. D. Anderson Cancer Center, Houston, TX.
  • Roger E. McLendon
    From the Duke University Medical Center, Durham, NC; and the University of Texas M. D. Anderson Cancer Center, Houston, TX.
  • Duane A. Mitchell
    From the Duke University Medical Center, Durham, NC; and the University of Texas M. D. Anderson Cancer Center, Houston, TX.
  • David A. Reardon
    From the Duke University Medical Center, Durham, NC; and the University of Texas M. D. Anderson Cancer Center, Houston, TX.
  • Raymond Sawaya
    From the Duke University Medical Center, Durham, NC; and the University of Texas M. D. Anderson Cancer Center, Houston, TX.
  • Robert J. Schmittling
    From the Duke University Medical Center, Durham, NC; and the University of Texas M. D. Anderson Cancer Center, Houston, TX.
  • Weiming Shi
    From the Duke University Medical Center, Durham, NC; and the University of Texas M. D. Anderson Cancer Center, Houston, TX.
  • James J. Vredenburgh
    From the Duke University Medical Center, Durham, NC; and the University of Texas M. D. Anderson Cancer Center, Houston, TX.
  • Darell D. Bigner
    From the Duke University Medical Center, Durham, NC; and the University of Texas M. D. Anderson Cancer Center, Houston, TX.

説明

<jats:sec><jats:title>Purpose</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> 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). </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> EGFRvIII-targeted vaccination in patients with GBM warrants investigation in a phase III, randomized trial. </jats:p></jats:sec>

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