Kaitlin M Peace, MD1, Diane F Hale, MD1, Timothy J Vreeland, MD2, Doreen O Jackson, MD1, Julia M Greene, MD1, John S Berry, MD3, Alfred F Trappey, MD4, Garth S Herbert, MD1, Guy T Clifton, MD1, Mark O Hardin, MD5, Kathleen M Darcy, PhD6, Chad A Hamilton, MD6, G. Larry Maxwell, MD6, George E Peoples, MD7. 1Brooke Army Medical Center, 2Womack Army Medical Center, 3Washington University Department of Colon and Rectal Surgery, 4David Grant USAF Medical Center, 5Madigan Army Medical Center, 6Gynecologic Cancer Center of Excellence, 7Cancer Vaccine Development Program
Objectives: Folate Binding Protein (FBP) is over-expressed on ovarian and endometrial cancer cells (up to 80-90-fold higher) and increased FBP expression (FBPe) is associated with aggressive disease. We are conducting a phase I/IIa trial of E39+GM-CSF, an HLA-A2-restricted, FBP-derived peptide vaccine to prevent clinical recurrences in disease-free patients. We have shown that E39 is safe, immunogenic, and may improve DFS when optimally dosed. Little is known about the effects of FBPe on FBP-directed therapies, including our E39 vaccine. Here, we report clinical outcomes based on FBPe.
Methods: Disease-free, HLA-A2+ patients were vaccinated (VG), while HLA-A2- patients were followed as controls (CG). VG received 6 monthly inoculations of E39+GM-CSF (either 100, 500, or 1000mcg of peptide and 250mcg of GM-CSF). FBPe testing was performed by immunohistochemistry and results were graded based on the percentage of positively staining cells; 0-1 categorized low expression (FBPlo), 2-4 categorized high expression (FBPhi). Patients were monitored for evidence of clinical recurrence through SOC follow-up by their treating team. Demographics, FBP expression and disease-free survival (DFS) were analyzed.
Results: Thirty-eight enrolled patients underwent FBPe testing (CG n=20; VG n=18). There were no clinicopathologic differences between groups (p≥0.1). Nineteen patients were FBPlo (CG, n=11; VG, n=8) and 19 were FBPhi (CG, n=9; VG, n=10). Median follow up was 16.3 months. There was no significant difference in overall DFS between the CG and the VG (34.6% vs. 34.6%, p=0.208). In FBPlo, there was improved DFS in the VG vs. CG (85.7% vs. 17.5%, p=0.01) while there was no such difference in FBPhi (VG:13.9% vs. CG:44.4%, p=0.83). Among FBPlo patients, there was a dose-dependent effect on DFS with patients receiving 1000mcg having improved DFS vs. <1000mcg and CG (100% vs. 66.7% vs. 17.5%, p=0.03).
Conclusion: This phase I/IIa trial has previously demonstrated that E39 is well-tolerated, elicits a strong in vivo immune response and may improve DFS when properly dosed. This focused analysis based on FBPe revealed a DFS benefit in FBPlo, but not FBPhi patients treated with E39. This may be due to immunotolerance from higher endogenous exposure to FBP in FBPhi patients. This is concordant with breast cancer peptide-based trials with differential efficacy based on HER2 expression and warrants further evaluation of E39+GM-CSF in FBPlo patients.
Presented at the SAGES 2017 Annual Meeting in Houston, TX.
Abstract ID: 80269
Program Number: MSS06
Presentation Session: Full-Day Military Surgical Symposium – General Surgery Presentations
Presentation Type: MSSPodium