P5-16-02 Final Results of the Phase I/II Trials of the E75 Adjuvant Breast Cancer Vac

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P5-16-02
Final Results of the Phase I/II Trials of the E75 Adjuvant Breast
Cancer Vaccine
Vreeland TJ, Clifton GT, Hale DF, Sears AK, Patil R, Holmes JP,
Ponniah S, Mittendorf EA, Peoples GE. San Antonio Military Medical
Center, San Antonio, TX; Joyce Murtha Breast Care Center, Windber,
PA; Redwood Regional Medical Group, Santa Rosa Memorial
Hospital, Santa Rosa, CA; Uniform Services University of Health
Sciences, Bethesda, MD; MD Anderson Cancer Center, Houston, TX
Background: We have completed phase I/II clinical trials vaccinating
breast cancer patients (pts) with E75, a HLA-A2/A3-restricted HER2/
neu (HER2) peptide vaccine. The vaccine was administered in the
adjuvant setting to prevent recurrences in high risk patients rendered
disease-free with standard of care therapy. We have previously
reported preliminary results indicating that the vaccine (including
booster inoculations) is safe and effective in stimulating an antitumor
immune response. Here, we report the final 5 year results
from these trials.
Methods: The phase I/II trials were performed as dose-escalation/
schedule-optimization trials enrolling node positive and high-risk,
node negative breast cancer patients with tumors expressing any level
of HER2. HLA-A2/A3+ pts were enrolled into the vaccine group
(VG) while HLA-A2/A3- pts were followed prospectively as the
untreated control group (CG). The VG pts were given 4-6 monthly
intradermal inoculations of E75 with GM-CSF during the primary
vaccine series (PVS). In addition, a voluntary booster program was
initiated during the trial, with booster inoculations being offered every
6 months after completion of the PVS. Patients were monitored for
local and systemic toxicity (graded by NCI Common Terminology
Criteria for Adverse Events). In vivo immune response was assessed
in the VG by delayed type hypersensitivity (DTH) reactions to both
E75 and saline, pre- and post-PVS. VG and CG pts were followed
for 60 months (mo) and recurrences were documented. Demographic
differences were compared with the Fisher’s exact test and diseasefree
survival was determined using the Kaplan-Meier method and
compared by log-rank test.
Results: 195 pts were enrolled, 6 withdrew (2 from VG, 4 from CG),
1 was lost to follow-up prior to vaccination, and 1 was found to be
ineligible, leaving 187 evaluable pts; 108 in the VG and 79 in the
CG. 53 pts volunteered for the booster program and received at least
one booster inoculation. The VG and CG were well-matched with the
only statistically significant difference being ER-/PR- status (31.1%
in VG vs 17.7% in CG, p=0.04). Vaccination was well tolerated
(maximum local toxicity: 73.1% Grade 1, 26.9% Grade 2, 0% Grade
3; maximum systemic toxicity: 72.2% Grade 1, 15.7% Grade 2, and
2.8% Grade 3). In the VG, pre- to post-PVS E75 DTH significantly
increased (mean 3.8 ±1.0 vs 14.8±1.4, p<0.001) and post-PVS E75
DTH was significantly greater than post-PVS saline DTH (1.84±0.5
vs 14.8±1.4, p<0.001). At the end of the trial, analysis of the Kaplan
Meier curves at 60 mo shows increased disease-free survival in the
VG compared to the CG with a trend toward significance (89.7% vs
80.6%, p=0.076).
Conclusions: The E75 breast cancer vaccine is safe and well–
tolerated. It elicits strong immune responses in vaccinated patients. At the end of the 5 year follow-up period, the E75 vaccine shows a
strong trend toward preventing breast cancer recurrence in vaccinated
patients. To investigate this vaccine (now known as NeuVax) further,
the PRESENT trial, a prospective, randomized, double-blind, placebocontrolled,
multi-center phase III registration trial has been initiated
and is actively enrolling.