title: Final report of the phase I/II clinical trial of the E75 (nelipepimut-S) vaccine with booster inoculations to prevent disease recurrence in high-risk breast cancer patients.
abstract: BACKGROUND
  E75 (nelipepimut-S) is a human leukocyte antigen (HLA)-A2/A3-restricted immunogenic peptide derived from the HER2 protein. We have conducted phase I/II clinical trials vaccinating breast cancer patients with nelipepimut-S and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the adjuvant setting to prevent disease recurrence. All patients have completed 60 months follow-up, and here, we report the final analyses.
  
  
  METHODS
  The studies were conducted as dose escalation/schedule optimization trials enrolling node-positive and high-risk node-negative patients with tumors expressing any degree of HER2 (immunohistochemistry 1-3+). HLA-A2/3+ patients were vaccinated; others were followed prospectively as controls. Local and systemic toxicity was monitored. Clinical recurrences were documented, and disease-free survival (DFS) was analyzed by Kaplan-Meier curves; groups were compared using log-rank tests.
  
  
  RESULTS
  Of 195 enrolled patients, 187 were assessable: 108 (57.8%) in the vaccinated group (VG) and 79 (42.2%) in the control group (CG). The groups were well matched for clinicopathologic characteristics. Toxicities were minimal. Five-year DFS was 89.7% in the VG versus 80.2% in the CG (P = 0.08). Due to trial design, 65% of patients received less than the optimal vaccine dose. Five-year DFS was 94.6% in optimally dosed patients (P = 0.05 versus the CG) and 87.1% in suboptimally dosed patients. A voluntary booster program was initiated, and among the 21 patients that were optimally boosted, there was only one recurrence (DFS = 95.2%).
  
  
  CONCLUSIONS
  The E75 vaccine is safe and appears to have clinical efficacy. A phase III trial evaluating the optimal dose and including booster inoculations has been initiated.
  
  
  RESULTS
  NCT00841399, NCT00584789.
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: E A
authors.initials: EA
authors.lastname: Mittendorf
authors.affiliation: Blanchfield Army Community Hospital, Fort Campbell.
authors.forename: G T
authors.initials: GT
authors.lastname: Clifton
authors.affiliation: Redwood Regional Medical Group, Santa Rosa.
authors.forename: J P
authors.initials: JP
authors.lastname: Holmes
authors.affiliation: Department of Surgery, Brooke Army Medical Center, Ft Sam Houston.
authors.forename: E
authors.initials: E
authors.lastname: Schneble
authors.affiliation: Department of Hematology Oncology, Walter Reed Army Medical Center, Washington.
authors.forename: D
authors.initials: D
authors.lastname: van Echo
authors.affiliation: Department of Surgery, Cancer Vaccine Development Program, United States Military Cancer Institute, Uniformed Services University of the Health Sciences, Bethesda, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ponniah
authors.affiliation: Department of Surgery, Brooke Army Medical Center, Ft Sam Houston; Department of Surgery, Cancer Vaccine Development Program, United States Military Cancer Institute, Uniformed Services University of the Health Sciences, Bethesda, USA. Electronic address: george.peoples@us.army.mil.
authors.forename: G E
authors.initials: GE
authors.lastname: Peoples
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000276:immunology*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use; D015789:HLA-A2 Antigen / Q000276:immunology; D015791:HLA-A3 Antigen / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D007167:Immunotherapy / Q000379:methods*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015789:HLA-A2 Antigen; D015791:HLA-A3 Antigen; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: breast cancer; immunotherapy; nelipepimut-S; vaccine