PMID- 24907636 OWN - NLM STAT- MEDLINE DCOM- 20150608 LR - 20240507 IS - 1569-8041 (Electronic) IS - 0923-7534 (Print) IS - 0923-7534 (Linking) VI - 25 IP - 9 DP - 2014 Sep TI - 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. PG - 1735-1742 LID - S0923-7534(19)35100-2 [pii] LID - 10.1093/annonc/mdu211 [doi] AB - 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. CI - (c) 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. FAU - Mittendorf, E A AU - Mittendorf EA AD - Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston. FAU - Clifton, G T AU - Clifton GT AD - Blanchfield Army Community Hospital, Fort Campbell. FAU - Holmes, J P AU - Holmes JP AD - Redwood Regional Medical Group, Santa Rosa. FAU - Schneble, E AU - Schneble E AD - Department of Surgery, Brooke Army Medical Center, Ft Sam Houston. FAU - van Echo, D AU - van Echo D AD - Department of Hematology Oncology, Walter Reed Army Medical Center, Washington. FAU - Ponniah, S AU - Ponniah S AD - Department of Surgery, Cancer Vaccine Development Program, United States Military Cancer Institute, Uniformed Services University of the Health Sciences, Bethesda, USA. FAU - Peoples, G E AU - Peoples GE AD - 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. Electronic address: george.peoples@us.army.mil. LA - eng SI - ClinicalTrials.gov/NCT00584789 SI - ClinicalTrials.gov/NCT00841399 GR - P30 CA016672/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140606 PL - England TA - Ann Oncol JT - Annals of oncology : official journal of the European Society for Medical Oncology JID - 9007735 RN - 0 (Adjuvants, Immunologic) RN - 0 (Cancer Vaccines) RN - 0 (HLA-A2 Antigen) RN - 0 (HLA-A3 Antigen) RN - 0 (Peptide Fragments) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM CIN - Nat Rev Clin Oncol. 2014 Aug;11(8):440. PMID: 24958184 MH - Adjuvants, Immunologic/therapeutic use MH - Adult MH - Aged MH - Breast/pathology MH - Breast Neoplasms/*immunology MH - Cancer Vaccines/adverse effects/*therapeutic use MH - Disease-Free Survival MH - Female MH - Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage/therapeutic use MH - HLA-A2 Antigen/immunology MH - HLA-A3 Antigen/immunology MH - Humans MH - Immunization, Secondary MH - Immunotherapy/*methods MH - Middle Aged MH - Neoplasm Recurrence, Local/*prevention & control MH - Peptide Fragments/administration & dosage/immunology MH - Receptor, ErbB-2/*immunology/metabolism MH - Vaccination PMC - PMC4143091 OTO - NOTNLM OT - breast cancer OT - immunotherapy OT - nelipepimut-S OT - vaccine EDAT- 2014/06/08 06:00 MHDA- 2015/06/09 06:00 PMCR- 2015/09/01 CRDT- 2014/06/08 06:00 PHST- 2014/06/08 06:00 [entrez] PHST- 2014/06/08 06:00 [pubmed] PHST- 2015/06/09 06:00 [medline] PHST- 2015/09/01 00:00 [pmc-release] AID - S0923-7534(19)35100-2 [pii] AID - mdu211 [pii] AID - 10.1093/annonc/mdu211 [doi] PST - ppublish SO - Ann Oncol. 2014 Sep;25(9):1735-1742. doi: 10.1093/annonc/mdu211. Epub 2014 Jun 6.