Primary analysis of the prospective, randomized, phase II trial of GP2+GM-CSF vaccine versus GM-CSF alone administered in the adjuvant setting to high-risk breast cancer patients.

Systemic Therapy
Session Type and Session Title: 
Oral Abstract Session B: Risk Assessment, Prevention, Early Detection, Screening, and Systemic Therapy
General Poster Session B: Risk Assessment, Prevention, Early Detection,  Screening, and Systemic Therapy
Abstract Number: 
J Clin Oncol 32, 2014 (suppl 26; abstr 134)
Erika J Schneble, Sonia A. Perez, James L. Murray, John S. Berry, Alfred F. Trappey, Timothy J. Vreeland, Diane F. Hale, Julia M. Greene, Guy T. Clifton, Alexandros Ardavanis, Jennifer Keating Litton, Sathibalan Ponniah, Nathan M. Shumway, Michael Papamichail, George Earl Peoples, Elizabeth Ann Mittendorf; San Antonio Military Medical Center, San Antonio, TX; Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Athens, Greece; The University of Texas MD Anderson Cancer Center, Houston, TX; Saint Savvas Anticancer Hospital, Athens, Greece; Cancer Vaccine Development Program, United States Military Cancer Institute, USUHS, Bethesda, MD; Cancer Immunology and Immunotherapy Center, Athens, Greece; San Antonio Military Medical Center, Fort Sam Houston, TX

Abstract Disclosures


Background: GP2 is a HER2 derived, HLA-A2+-restricted immunogenic peptide designed to stimulate CD8+T cells to recognize tumor cells with any level of HER2 expression (IHC 1-3+). Accrual to a prospective, randomized, multi-center, phase II trial of the GP2 vaccine for prevention of breast cancer recurrence has completed. Here, the planned primary analysis of disease-free survival (DFS) is presented. Methods: HLA-A2+ node positive or high-risk node negative breast cancer patients (pts) with any level of HER2 expression rendered disease-free by standard of care therapy (to include trastuzumab where appropriate) were randomized to receive GP2+GM-CSF (VG) or GM-CSF (CG) alone. Pts received 6 monthly inoculations (primary vaccine series = PVS) followed by 4 boosters administered every 6 months. The Kaplan Meier method was used for statistical analysis. The intention-to-treat (ITT) population is defined as the entire randomly assigned population. The per-treatment (PT) group excluded pts who recurred during the PVS or developed a second malignancy. A pre-specified subgroup analysis was performed based on HER2 expression level. HER2 overexpression (OE) is defined as IHC 3+or FISH >2.2. Results: With 89 VG and 91 CG pts enrolled and vaccinated, there are no differences between groups with respect to age, node positivity, tumor size, grade, ER/PR status, and HER2 expression (p>0.05). The vaccine has been well tolerated with toxicities comparable between the VG and CG. Only one grade 3 local and systemic toxicity reaction has been reported in the VG. At 34 (1-60) month median follow-up, DFS was compared in the ITT (85% VG v 81% CG, p = 0.57) and PT (94% VG v 85% CG, p = 0.17) populations. In OE patients (51 VG and 50 CG) DFS was 94% VG v 89% CG, p = 0.86 (ITT) and 100% VG v 89% CG, p = 0.08 (PT). Conclusions: GP2+GM-CSF is a novel vaccine that is safe and well tolerated. This phase II trial demonstrates potentially greater benefit in pts with HER2 OE tumors, in whom there have been no recurrences in the PT group. This may be due to synergism with trastuzumab therapy, thus justifying a phase III trial evaluating GP2 administered in the adjuvant setting to a HER2 OE population. Clinical trial information: NCT00524277.