Tommy A Brown, MD1, John W Myers, MD1, Kaitlin M Peace, MD1, Jennifer K Litton, MD2, Rashmi Murthy, MD3, Timothy J Vreeland, MD2, Diane F Hale, MD1, Garth S Herbert, MD1, Guy T Clifton, MD1, Mark O Hardin, MD4, George E Peoples, MD5, Elizabeth A Mittendorf, MD2. 1Department of Surgery, Brooke Army Medical Center, 2The University of Texas MD Anderson Cancer Center, 3Department of Surgery, Womack Army Medical Center, 4Department of Surgery, Madigan Army Medical Center, 5Cancer Vaccine Development Program
Introduction: Trastuzumab (Tz), a HER2-targeted monoclonal antibody, is standard of care (SOC) for HER2+ breast cancer (BCa) & decreases recurrence. We have previously shown that the HER2-targeted peptide vaccine E75 + GM-CSF (NeuVax) is safe, immunogenic, & may have synergistic clinical efficacy in combination with Tz. The known cardiac toxicity of Tz raises the concern that adding a HER2-directed vaccine to Tz may worsen this complication. We are enrolling patients (pts) in a placebo-controlled, prospective, multi-center, randomized, single-blinded phase II trial of Tz + E75 in the adjuvant setting to reduce recurrence in HER2+ BCa pts. Presented here are the initial safety data.
Methods: Pts with stage I-III, HER2+, HLA-A2/A3+ BCa at high risk for recurrence (without a complete response after neoadjuvant Tz or those undergoing up-front surgery with node-positive disease if ER/PR- or ≥4 positive nodes if ER/PR+) were enrolled after SOC surgery, neo-adjuvant/adjuvant chemotherapy with approved Tz-containing regimen, & radiation. Pts were randomized to receive Tz & E75 (vaccine group; VG) or Tz & GM-CSF (control group: CG). Pts were inoculated with E75 or GM-CSF intradermally every 3 weeks for 6 total vaccinations (primary vaccine series; PVS) starting with the third dose of Tz maintenance therapy. After 6 months from the completion of the PVS pts received a booster inoculation every 6 months for 2 years (4 total). Cardiac ejection fraction (EF) was measured either by MUGA or echo at baseline then serially while enrolled. Safety & demographic data were collected & analyzed. Safety analysis began after enrollment of the 50th patient.
Results: 50 pts have been enrolled to date (VG n=22, CG n=28). No significant clinicopathologic differences were found between groups. No related grade 4 or 5 toxicities & no differences in related toxicities occurred in the VG vs CG (Grade 1: 96% vs 98.5%; Grade 2: 3.2% vs 1.5%; Grade 3: 0.8% vs 0%, p=0.14). No significant reduction in EF pre- vs post-treatment was found (VG: 61.1±5.4% vs 60.1±4.8%, p=0.55; CG: 62.3±5.7% vs 61.9±4.0%, p=0.74) & there was no difference in EF changes between groups (p=0.54).
Conclusion: The Tz + E75 combination in HER2+ BCa pts was tolerated well & the cardiac affects from Tz were not worsened by the addition of E75. Enrollment in this trial will continue to a goal of 100 pts & a report of immunologic & clinical outcomes is planned in the primary analysis after 24-months of follow-up.
Presented at the SAGES 2017 Annual Meeting in Houston, TX.
Abstract ID: 88035
Program Number: MSS17
Presentation Session: Full-Day Military Surgical Symposium – General Surgery Presentations
Presentation Type: MSSPodium