title: Primary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide AE37 vaccine in breast cancer patients to prevent recurrence.
abstract: AE37 is the Ii-Key hybrid of the MHC class II peptide, AE36 (HER2 aa:776-790). Phase I studies showed AE37 administered with granulocyte macrophage colony-stimulating factor (GM-CSF) to be safe and highly immunogenic. A prospective, randomized, multicenter phase II adjuvant trial was conducted to evaluate the vaccine's efficacy.
  
  
  
  Clinically disease-free node-positive and high-risk node-negative breast cancer patients with tumors expressing any degree of HER2 [immunohistochemistry (IHC) 1-3+] were enrolled. Patients were randomized to AE37 + GM-CSF versus GM-CSF alone. Toxicity was monitored. Clinical recurrences were documented and disease-free survival (DFS) analyzed.
  
  
  
  The trial enrolled 298 patients; 153 received AE37 + GM-CSF and 145 received GM-CSF alone. The groups were well matched for clinicopathologic characteristics. Toxicities have been minimal. At the time of the primary analysis, the recurrence rate in the vaccinated group was 12.4% versus 13.8% in the control group [relative risk reduction 12%, HR 0.885, 95% confidence interval (CI) 0.472-1.659, P = 0.70]. The Kaplan-Meier estimated 5-year DFS rate was 80.8% in vaccinated versus 79.5% in control patients. In planned subset analyses of patients with IHC 1+/2+ HER2-expressing tumors, 5-year DFS was 77.2% in vaccinated patients (n = 76) versus 65.7% in control patients (n = 78) (P = 0.21). In patients with triple-negative breast cancer (HER2 IHC 1+/2+ and hormone receptor negative) DFS was 77.7% in vaccinated patients (n = 25) versus 49.0% in control patients (n = 25) (P = 0.12).
  
  
  
  The overall intention-to-treat analysis demonstrates no benefit to vaccination. However, the results confirm that the vaccine is safe and suggest that vaccination may have clinical benefit in patients with low HER2-expressing tumors, specifically TNBC. Further evaluation in a randomized trial enrolling TNBC patients is warranted.
authors.affiliation: Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA eamitten@mdanderson.org.
authors.forename: E A
authors.initials: EA
authors.lastname: Mittendorf
authors.affiliation: Cancer Immunology and Immunotherapy Center, St Savas Cancer Hospital, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Ardavanis
authors.affiliation: Department of Cancer Biostatistics, Levine Cancer Institute, Charlotte.
authors.forename: J
authors.initials: J
authors.lastname: Symanowski
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: J L
authors.initials: JL
authors.lastname: Murray
authors.affiliation: Department of Hematology/Oncology, Brooke Army Medical Center, Ft Sam Houston Cancer Vaccine Development Laboratory, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda.
authors.forename: N M
authors.initials: NM
authors.lastname: Shumway
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: J K
authors.initials: JK
authors.lastname: Litton
authors.affiliation: Department of Surgery, Brooke Army Medical Center, Ft Sam Houston.
authors.forename: D F
authors.initials: DF
authors.lastname: Hale
authors.affiliation: Cancer Immunology and Immunotherapy Center, St Savas Cancer Hospital, Athens, Greece.
authors.forename: S A
authors.initials: SA
authors.lastname: Perez
authors.affiliation: Cancer Immunology and Immunotherapy Center, St Savas Cancer Hospital, Athens, Greece.
authors.forename: E A
authors.initials: EA
authors.lastname: Anastasopoulou
authors.affiliation: Cancer Immunology and Immunotherapy Center, St Savas Cancer Hospital, Athens, Greece.
authors.forename: N F
authors.initials: NF
authors.lastname: Pistamaltzian
authors.affiliation: Cancer Vaccine Development Laboratory, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda.
authors.forename: S
authors.initials: S
authors.lastname: Ponniah
authors.affiliation: Cancer Immunology and Immunotherapy Center, St Savas Cancer Hospital, Athens, Greece.
authors.forename: C N
authors.initials: CN
authors.lastname: Baxevanis
authors.affiliation: Antigen Express, Worcester.
authors.forename: E
authors.initials: E
authors.lastname: von Hofe
authors.affiliation: Cancer Immunology and Immunotherapy Center, St Savas Cancer Hospital, Athens, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Papamichail
authors.affiliation: Cancer Vaccine Development Program, San Antonio Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, USA.
authors.forename: G E
authors.initials: GE
authors.lastname: Peoples
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D010446:Peptide Fragments / Q000276:immunology / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D064726:Triple Negative Breast Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; C530655:AE37 vaccine; C508053:ERBB2 protein, human
keywords: HER2; breast cancer; immunotherapy; triple-negative breast cancer; vaccine