Primary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide AE37 vaccine in breast cancer patients to prevent recurrence

Ann Oncol. 2016 Jul;27(7):1241-8. doi: 10.1093/annonc/mdw150. Epub 2016 Mar 30.


Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: HER2; breast cancer; immunotherapy; triple-negative breast cancer; vaccine.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adult
  • Aged
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / adverse effects
  • Disease-Free Survival
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / prevention & control
  • Peptide Fragments / immunology
  • Peptide Fragments / therapeutic use
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / immunology*
  • Triple Negative Breast Neoplasms / immunology
  • Triple Negative Breast Neoplasms / pathology
  • Triple Negative Breast Neoplasms / prevention & control*


  • AE37 vaccine
  • Adjuvants, Immunologic
  • Cancer Vaccines
  • Peptide Fragments
  • ERBB2 protein, human
  • Receptor, ErbB-2