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Ann Oncol. 2014 Sep;25(9):1735-42. doi: 10.1093/annonc/mdu211. Epub 2014 Jun 6.

Final report of the phase I/II clinical trial of the E75 (nelipepimut-S) vaccine with booster inoculations to prevent disease recurrence in high-risk breast cancer patients.

Author information

1
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston.
2
Blanchfield Army Community Hospital, Fort Campbell.
3
Redwood Regional Medical Group, Santa Rosa.
4
Department of Surgery, Brooke Army Medical Center, Ft Sam Houston.
5
Department of Hematology Oncology, Walter Reed Army Medical Center, Washington.
6
Department of Surgery, Cancer Vaccine Development Program, United States Military Cancer Institute, Uniformed Services University of the Health Sciences, Bethesda, USA.
7
Department of Surgery, Brooke Army Medical Center, Ft Sam Houston Department of Surgery, Cancer Vaccine Development Program, United States Military Cancer Institute, Uniformed Services University of the Health Sciences, Bethesda, USA george.peoples@us.army.mil.

Abstract

BACKGROUND:

E75 (nelipepimut-S) is a human leukocyte antigen (HLA)-A2/A3-restricted immunogenic peptide derived from the HER2 protein. We have conducted phase I/II clinical trials vaccinating breast cancer patients with nelipepimut-S and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the adjuvant setting to prevent disease recurrence. All patients have completed 60 months follow-up, and here, we report the final analyses.

PATIENTS AND METHODS:

The studies were conducted as dose escalation/schedule optimization trials enrolling node-positive and high-risk node-negative patients with tumors expressing any degree of HER2 (immunohistochemistry 1-3+). HLA-A2/3+ patients were vaccinated; others were followed prospectively as controls. Local and systemic toxicity was monitored. Clinical recurrences were documented, and disease-free survival (DFS) was analyzed by Kaplan-Meier curves; groups were compared using log-rank tests.

RESULTS:

Of 195 enrolled patients, 187 were assessable: 108 (57.8%) in the vaccinated group (VG) and 79 (42.2%) in the control group (CG). The groups were well matched for clinicopathologic characteristics. Toxicities were minimal. Five-year DFS was 89.7% in the VG versus 80.2% in the CG (P = 0.08). Due to trial design, 65% of patients received less than the optimal vaccine dose. Five-year DFS was 94.6% in optimally dosed patients (P = 0.05 versus the CG) and 87.1% in suboptimally dosed patients. A voluntary booster program was initiated, and among the 21 patients that were optimally boosted, there was only one recurrence (DFS = 95.2%).

CONCLUSION:

The E75 vaccine is safe and appears to have clinical efficacy. A phase III trial evaluating the optimal dose and including booster inoculations has been initiated.

CLINICAL TRIALS:

NCT00841399, NCT00584789.

KEYWORDS:

breast cancer; immunotherapy; nelipepimut-S; vaccine

PMID:
24907636
PMCID:
PMC4143091
DOI:
10.1093/annonc/mdu211
[Indexed for MEDLINE]
Free PMC Article

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