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

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. Cancer 2011. © 2011 American Cancer Society.