Abstract P5-18-07: Completed SN33 Trial: 60 month follow-up of Early Stage Node Positive HER2 Negative patients with NeuVax ™(E75) and sargramostim.

Abstract

Abstract Background: Despite recent advances in adjuvant treatment, the prognosis for HER2 negative patients has not improved. Unlike HER2 positive patients, the benefit of Herceptin has not been shown. Here we present the final 60-month results of a phase 1/I2 clinical trial vaccinating early stage node positive breast cancer patients with NeuVax (E75) and sargramostim following adjuvant chemotherapy and radiation. Previously, data reported from this trial was combined with a node negative trial that used the same treatment schema. Those reports showed the vaccine was safe, and effective at stimulating HER2-specific immunity. We report safety and efficacy (Disease Free Survival, DFS) data through 60 months. Methods: Eligible patients had excised early stage node-positive breast cancer with any level of HER2 expression. After completion of standard of care chemotherapy and radiation, patients were enrolled but not randomized: patients were assigned to the vaccine group (VG) only if they were HLA A2/A3+. The non-treated patients were followed as a control group (CG). Hormone receptor positive patients received appropriate adjuvant therapy concomitant with vaccine. The phase I/II trial was performed with phase 1 as a dose escalation/schedule optimization where VG was given 3–6 monthly inoculations of NeuVax (E75) with the immunoadjuvant, sargramostim. The phase 2 portion utilized the optimal dose and schedule carried forward. Herceptin became commercially available during the conduct of the trial, and HER2 positive patients were offered this treatment but remained on trial. DFS was summarized by Kaplan-Meier lifetables and analyzed by the log-rank test. Due to waning immunity after the scheduled monthly vaccinations, a voluntary booster program was initiated to be integrated into the trial process. Results: 97 patients were enrolled; 53 in the VG and 44 in the CG. The VG and CG were well-matched with the only difference being trastuzumab therapy (18.5% in VG vs. 4.8% in CG, p = 0.03). There were no HER2 0 patients in the VG. Vaccination was well tolerated with primarily grade 1 and grade 2 toxicity. No VG patients relapsed during the vaccination period. ITT patients in this phase 1/2 trial favored VG in DFS at 24 months (VG 90.6%, CG 79.5%, p = 0.1194); at 60 months, the VG continues to have fewer recurrences than the CG (VG 84.5% vs. 77.1%, p = 0.3046). In the patients who were treated at the optimum (Phase 2) dose, the difference in the DFS at 24 months observed was (VG 96.2%, CG 79.5%, p = 0.0597); at 60 months, the VG continues to have fewer recurrences than the CG (92.3% vs. 77.1%). When the HER2 positive patients were removed from the population, the Phase 2 HER2 Negative VG had a significantly improved DFS at 24 months (100% vs. 80.6%, p = 0.045); at 60 months, VG retains a 17% difference (VG 94.7% vs. CG 77.4%). Conclusions: NeuVax (E75) and sargramostim vaccine is safe and well–tolerated in early stage breast cancer patients. With follow-up at 60 months, the vaccine used as adjuvant therapy continues to reduce relapses in node positive HER2 negative patients treated at an optimal dose. A phase 3 multicenter, multinational double-blind trial is underway. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-18-07.