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

Publication ,  Journal Article
Sampson, JH; Heimberger, AB; Archer, GE; Aldape, KD; Friedman, AH; Friedman, HS; Gilbert, MR; Herndon, JE; McLendon, RE; Mitchell, DA; Shi, W ...
Published in: J Clin Oncol
November 1, 2010

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.

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Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

November 1, 2010

Volume

28

Issue

31

Start / End Page

4722 / 4729

Location

United States

Related Subject Headings

  • United States
  • Tumor Suppressor Proteins
  • Time Factors
  • Temozolomide
  • Sample Size
  • Radiotherapy, Adjuvant
  • Prospective Studies
  • Prognosis
  • Predictive Value of Tests
  • Oncology & Carcinogenesis
 

Citation

APA
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Sampson, J. H., Heimberger, A. B., Archer, G. E., Aldape, K. D., Friedman, A. H., Friedman, H. S., … Bigner, D. D. (2010). Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J Clin Oncol, 28(31), 4722–4729. https://doi.org/10.1200/JCO.2010.28.6963
Sampson, John H., Amy B. Heimberger, Gary E. Archer, Kenneth D. Aldape, Allan H. Friedman, Henry S. Friedman, Mark R. Gilbert, et al. “Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma.J Clin Oncol 28, no. 31 (November 1, 2010): 4722–29. https://doi.org/10.1200/JCO.2010.28.6963.
Sampson JH, Heimberger AB, Archer GE, Aldape KD, Friedman AH, Friedman HS, et al. Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J Clin Oncol. 2010 Nov 1;28(31):4722–9.
Sampson, John H., et al. “Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma.J Clin Oncol, vol. 28, no. 31, Nov. 2010, pp. 4722–29. Pubmed, doi:10.1200/JCO.2010.28.6963.
Sampson JH, Heimberger AB, Archer GE, Aldape KD, Friedman AH, Friedman HS, Gilbert MR, Herndon JE, McLendon RE, Mitchell DA, Reardon DA, Sawaya R, Schmittling RJ, Shi W, Vredenburgh JJ, Bigner DD. Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J Clin Oncol. 2010 Nov 1;28(31):4722–4729.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

November 1, 2010

Volume

28

Issue

31

Start / End Page

4722 / 4729

Location

United States

Related Subject Headings

  • United States
  • Tumor Suppressor Proteins
  • Time Factors
  • Temozolomide
  • Sample Size
  • Radiotherapy, Adjuvant
  • Prospective Studies
  • Prognosis
  • Predictive Value of Tests
  • Oncology & Carcinogenesis