Clinical trial results of the HER-2/neu (E75) vaccine to prevent breast cancer recurrence in high-risk patients: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02

Abstract

Background: The authors conducted exploratory phase 1-2 clinical trials vaccinating breast cancer patients with E75, a human leukocyte antigen (HLA) A2/A3-restricted HER-2/neu (HER2) peptide, and granulocyte-macrophage colony-stimulating factor. The vaccine is given as adjuvant therapy to prevent disease recurrence. They previously reported that the vaccine is safe and effective in stimulating expansion of E75-specific cytotoxic T cells. Here, they report 24-month landmark analyses of disease-free survival (DFS).

Methods: These dose escalation/schedule optimization trials enrolled lymph node-positive and high-risk lymph node-negative patients with HER2 (immunohistochemistry [IHC] 1-3(+) ) expressing tumors. HLA-A2/A3(+) patients were vaccinated; others were followed prospectively as controls for recurrence. DFS was analyzed by Kaplan-Meier curves; groups were compared using log-rank tests.

Results: Of 195 enrolled patients, 182 were evaluable: 106 (58.2%) in the vaccinated group and 76 (41.8%) in the control group. The 24-month landmark analysis DFS was 94.3% in the vaccinated group and 86.8% in the control group (P = .08). Importantly, because of trial design, 65% of patients received a lower than optimal vaccine dose. In subset analyses, patients who benefited most from vaccination (vaccinated group vs control group) had lymph node-positive (DFS, 90.2% vs 79.1%; P = .13), HER2 IHC 1+-2+ (DFS, 94.0% vs 79.4%; P = .04), or grade 1 or 2 (DFS, 98.4% vs 86.0%; P = .01) tumors and were optimally dosed (DFS, 97.3% vs 86.8%; P = .08). A booster program has been initiated; no patients receiving booster inoculations have recurred.

Conclusions: The E75 vaccine has clinical efficacy that is more prominent in certain patients. A phase 3 trial enrolling lymph node-positive patients with HER2 low-expressing tumors is warranted.

Conflict of interest statement

CONFLICT OF INTEREST DISCLOSURES

G.E.P. has partial inventor rights to E75 (owned jointly by The University of Texas MD Anderson Cancer Center and the US Government), and the patent was licensed to Apthera, Inc., Scottsdale, Arizona, after completion of the described trials. Under the terms of the license, G.E.P. is entitled to licensing revenues, and he also serves as a consultant to Apthera.

Copyright © 2011 American Cancer Society.

Figures

Figure 1

E75 vaccine trial schema. IND = Investigational New Drug.

Figure 2

24-month disease-free survival for all vaccinated patients compared with unvaccinated control patients.

Figure 3

24-month disease-free survival (DFS) determined for clinicopathologic subgroups. DFS was compared between vaccinated patients and unvaccinated controls in patients with (A) node-positive breast cancer, (B) HER2 low-expressing (IHC 1+ or 2+ or FISH

Figure 4

24-month disease-free survival (DFS) based on dosing regimen. (A) patients who received the optimal dose were compared with unvaccinated controls. (B) patients who required dose reductions due to significant local reactions or ≥ grade 2 systemic toxicity were compared with unvaccinated contols. To date, no patient requiring a dose reduction has had disease recurrence.

Figure 5

24-month disease-free survival (DFS) comparing vaccinated patients who received booster inoculation with unvaccinated controls. (A) DFS comparing all vaccinated patients who received at least one booster inoculation prior to 24 months with unvaccinated controls. (B) DFs comparing vaccinated patients who received a booster 6 months after completing the primary vaccine series with unvaccinated controls, with patients having early recurrences (