Ann Oncol. 2014 Jun 6. pii: mdu211. [Epub ahead of print]
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.
Mittendorf EA1, Clifton GT2, Holmes JP3, Schneble E4, van Echo D5, Ponniah S6, Peoples GE7.
Author information
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 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 evaluable: 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=.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=.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.
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email:
journals.permissions@oup.com.
KEYWORDS:
Breast cancer; immunotherapy; nelipepimut-S; vaccine
PMID: 24907636 [