Optimal dose and schedule of an HER-2/neu (E75) peptide vaccine to prevent breast cancer recurrence: From US Military Cancer Institute Clinical Trials Group Study I-01 and I-02

Jarrod P. Holmes, Jeremy D. Gates, Linda C. Benavides, Matthew T. Hueman, Mark G. Carmichael, Ritesh Patil, Dianna Craig, Elizabeth A. Mittendorf, Alexander Stojadinovic, Sathibalan Ponniah, George E. Peoples

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND. E75, a HER-2/neu-derived peptide, was administered as a preventive vaccine with granulocyte-macrophage-colony-stimulating factor (GM-CSF) in disease-free lymph node-positive (NP) and lymph node-negative (NN) breast cancer (BCa) patients. The optimal biologic dose (OBD) was determined based on toxicity and immunologic response. METHODS. Patients were vaccinated over 6 months (3, 4, or 6 times) with different doses of E75 plus GM-CSF. Toxicities were graded per National Cancer Institute Common Terminology Criteria. GM-CSF was reduced for significant toxicity. Immunologic response was measured by delayed type hypersensitivity test (DTH), and E75-specific CD8 + T-cells were quantified with human leukocyte antigen-A2: immunoglobulin G dimer and flow cytometry. RESULTS. Ninety-nine patients (48 NP and 51 NN) were vaccinated in 7 dose groups. The OBD was 1000 lg E75 plus 250 μg GM-CSF monthly x 6. The optimal dose group (ODG, n = 29) experienced similar toxicities to the suboptimal dose group (SDG, n = 70), which was comprised of the remaining 6 groups. The ODG demonstrated a trend toward an increase in the average postvaccine dimer (0.87 ± 0.10% vs 0.67 ± 0.05%; P = .07), a significantly larger DTH response (21.5 ± 2.5 mm vs 11.3 ± 1.3 mm; P = .0002), and a trend toward decreased recurrences (3.4% vs 12.9%; P = .27). Compared with the SDG, the ODG had larger tumors (percentage ≥T2: 55% vs 23%; P = .004), more positive lymph nodes (percentage NP: 76% vs 37%; P = .001), and higher grade tumors (percentage grade 3: 52% vs 30%; P = .07), but a shorter median follow-up time (20 months vs 32 months; P <.001). CONCLUSIONS. Compared with suboptimally dosed patients, the optimally dosed E75 vaccine in disease-free BCa patients had similar toxicity but enhanced HER- 2/neu-specific immunity that may lead to decreased recurrences with additional follow-up.

Original languageEnglish (US)
Pages (from-to)1666-1675
Number of pages10
JournalCancer
Volume113
Issue number7
DOIs
StatePublished - Oct 1 2008

Keywords

  • Breast cancer
  • Dosing
  • E75
  • Peptide
  • Vaccine

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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