Abstract P2-09-01: Subgroups analysis of a multicenter, prospective, randomized, blinded phase 2b trial of trastuzumab + nelipeptimut-S (NeuVax) vs trastuzumab for prevention of recurrence in breast cancer patients
Authors: Clifton GT , Kemp Bohan PM , Hale DF , Myers JW , Brown TA , Holmes JP , Vreeland TJ , Litton JK , Murthy RK , Mittendorf EA , Peoples GE 
Published: May 2019

Abstract
Background:HER2 low-expressing (LE) (IHC 1-2+, FISH non-amplified) breast cancer (BC) patients (pts) have not benefited from HER2-directed therapy despite HER2 antigen availability. Triple negative BC (TNBC), in particular, is immunogenic and in need of additional therapeutic options. We have previously shown the HER2-derived nelipeptimut-S (E75) + GM-CSF (NeuVax) to be synergistic with trastuzumab (Tz) in pre-clinical and pilot clinical studies. In a planned interim analysis of a multi-center, prospective, randomized, single-blinded, placebo-controlled phase 2b trial of Tz + NeuVax vs Tz to reduce recurrence in HER2 LE, node-positive (NP) and/or triple negative BC (TNBC) pts, we previously reported that the NeuVax + Tz was safe without added cardiac toxicity and demonstrated a significant reduction of recurrences in TNBC pts. This analysis examines additional subsets in this trial.
Methods:HER2 LE, NP and/or TNBC pts who were clinically disease-free after standard therapy were randomized to receive Tz+NeuVax (vaccine group; VG) or Tz+GM-CSF (control group; CG). All pts received 1 yr of Tz per label. NeuVax or GM-CSF was given every 3 weeks x 6 starting with the 3rdTz dose, and then boosted every 6 months x 4. This pre-specified interim analysis was triggered 6 months after last enrollment. The primary endpoint is intention-to-treat 24 month disease-free survival (DFS) evaluated by log rank.
Results: Of 275 pts randomized in the study (VG n=136, CG n=139), 98 had TNBC (VG=53, CG=45). In the interim analysis, estimated disease-free survival (DFS) was assessed with a median follow up of 18.8 months. No significant clinicopathologic differences were seen between treatment groups. In the TNBC group, estimated DFS was higher overall in VG vs CG (91.9% v 69.9%, p=0.023; hazard ratio [HR] 0.29, 95% confidence interval [CI] 0.09-0.90). On TNBC subgroup analysis, estimated DFS was higher in VG vs CG among pts who received neoadjuvant chemotherapy (VG n=35, CG n=31; HR 0.26, CI 0.07-0.93; p=0.03), HER2 IHC 1+ BC (VG n=34, CG n=28; HR 0.20, CI 0.04-0.96; p=0.03), pts who were AJCC 7thedition stage I/II (VG n=37, CG n=27; HR incalculable, no recurrences in the VG, p=0.008), and pts 351yr of age (VG n=32 & CG n = 26; HR 0.26 CI 0.07,0.94; p=0.009). HRs did not appreciably vary based on the histologic grade or presence of lymphovascular invasion.
Conclusion:Examining the subgroups from the pre-specified interim analysis demonstrates a highly significant clinical benefit in TNBC pts overall. Within the TNBC cohort, specific benefit was seen in pts who received chemotherapy neoadjuvantly, expressed lower HER2, were earlier stage, and were older in age. These factors may help enrich the TNBC population targeted in a definitive Phase 3 study in TNBC patients with residual disease after neoadjuvant chemotherapy.
Citation Format: Clifton GT, Kemp Bohan PM, Hale DF, Myers JW, Brown TA, Holmes JP, Vreeland TJ, Litton JK, Murthy RK, Mittendorf EA, Peoples GE. Subgroups analysis of a multicenter, prospective, randomized, blinded phase 2b trial of trastuzumab + nelipeptimut-S (NeuVax) vs trastuzumab for prevention of recurrence in breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-09-01.