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): 4722-9, 2010 Nov 01.
Article
in En
| MEDLINE
| ID: mdl-20921459
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 ANDMETHODS:
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.
Full text:
1
Database:
MEDLINE
Main subject:
Brain Neoplasms
/
Glioblastoma
/
Cancer Vaccines
/
ErbB Receptors
Type of study:
Clinical_trials
/
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Country/Region as subject:
America do norte
Language:
En
Year:
2010
Type:
Article