PMID- 20921459
OWN - NLM
STAT- MEDLINE
DCOM- 20101109
LR  - 20231120
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 28
IP  - 31
DP  - 2010 Nov 1
TI  - Immunologic escape after prolonged progression-free survival with epidermal 
      growth factor receptor variant III peptide vaccination in patients with newly 
      diagnosed glioblastoma.
PG  - 4722-9
LID - 10.1200/JCO.2010.28.6963 [doi]
AB  - 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.
FAU - Sampson, John H
AU  - Sampson JH
AD  - Duke University Medical Center, Durham, NC 27710, USA.
FAU - Heimberger, Amy B
AU  - Heimberger AB
FAU - Archer, Gary E
AU  - Archer GE
FAU - Aldape, Kenneth D
AU  - Aldape KD
FAU - Friedman, Allan H
AU  - Friedman AH
FAU - Friedman, Henry S
AU  - Friedman HS
FAU - Gilbert, Mark R
AU  - Gilbert MR
FAU - Herndon, James E 2nd
AU  - Herndon JE 2nd
FAU - McLendon, Roger E
AU  - McLendon RE
FAU - Mitchell, Duane A
AU  - Mitchell DA
FAU - Reardon, David A
AU  - Reardon DA
FAU - Sawaya, Raymond
AU  - Sawaya R
FAU - Schmittling, Robert J
AU  - Schmittling RJ
FAU - Shi, Weiming
AU  - Shi W
FAU - Vredenburgh, James J
AU  - Vredenburgh JJ
FAU - Bigner, Darell D
AU  - Bigner DD
LA  - eng
GR  - P50 NS020023/NS/NINDS NIH HHS/United States
GR  - R01 CA097222/CA/NCI NIH HHS/United States
GR  - 5P50 NS20023/NS/NINDS NIH HHS/United States
GR  - R01-CA97222-05/CA/NCI NIH HHS/United States
GR  - 5P50 CA108786/CA/NCI NIH HHS/United States
GR  - R37 CA011898/CA/NCI NIH HHS/United States
GR  - R01 CA120813/CA/NCI NIH HHS/United States
GR  - P50 CA108786/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101004
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (epidermal growth factor receptor VIII)
RN  - 7GR28W0FJI (Dacarbazine)
RN  - EC 2.1.1.- (DNA Modification Methylases)
RN  - EC 2.1.1.63 (MGMT protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 6.5.1.- (DNA Repair Enzymes)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
CIN - J Clin Oncol. 2010 Nov 1;28(31):4670-3. PMID: 20921460
CIN - Nat Rev Clin Oncol. 2011 Jan;8(1):4. PMID: 21218529
CIN - J Clin Oncol. 2011 Jun 10;29(17):e517-8; author reply e519-20. PMID: 21555685
CIN - J Clin Oncol. 2011 Aug 1;29(22):3105; author reply 3105-6. PMID: 21709193
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents, Alkylating/therapeutic use
MH  - Brain Neoplasms/diagnosis/*drug 
      therapy/*immunology/mortality/radiotherapy/surgery
MH  - Cancer Vaccines/*immunology/*therapeutic use
MH  - Chemotherapy, Adjuvant
MH  - DNA Methylation
MH  - DNA Modification Methylases/genetics
MH  - DNA Repair Enzymes/genetics
MH  - Dacarbazine/analogs & derivatives/therapeutic use
MH  - Disease-Free Survival
MH  - Drug Administration Schedule
MH  - Enzyme-Linked Immunosorbent Assay
MH  - ErbB Receptors/*immunology
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Glioblastoma/diagnosis/*drug therapy/*immunology/mortality/radiotherapy/surgery
MH  - Humans
MH  - Immunohistochemistry
MH  - Injections, Intradermal
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Predictive Value of Tests
MH  - Prognosis
MH  - Prospective Studies
MH  - Radiotherapy, Adjuvant
MH  - Sample Size
MH  - Temozolomide
MH  - Time Factors
MH  - Tumor Suppressor Proteins/genetics
MH  - United States
PMC - PMC3020702
COIS- Authors' disclosures of potential conflicts of interest and author contributions 
      are found at the end of this article.
EDAT- 2010/10/06 06:00
MHDA- 2010/11/10 06:00
PMCR- 2011/11/01
CRDT- 2010/10/06 06:00
PHST- 2010/10/06 06:00 [entrez]
PHST- 2010/10/06 06:00 [pubmed]
PHST- 2010/11/10 06:00 [medline]
PHST- 2011/11/01 00:00 [pmc-release]
AID - JCO.2010.28.6963 [pii]
AID - 86963 [pii]
AID - 10.1200/JCO.2010.28.6963 [doi]
PST - ppublish
SO  - J Clin Oncol. 2010 Nov 1;28(31):4722-9. doi: 10.1200/JCO.2010.28.6963. Epub 2010 
      Oct 4.