P1-13-01: An Update of a Phase II Trial of the HER2 Peptide AE37 Vaccine in Breast Cancer Patients To Prevent Recurrence.
Authors: Hale DF , Perez S , Sears AK , Clifton GT , Vreeland TJ , Holmes JP , Ardavanis A , Pistamaltzian N , Rellias G , Ponniah S , Papamichail M , Peoples GE , Mittendorf EA 
Published: June 2012

Abstract
Introduction AE37 is the Ii-Key hybrid of the HER2−derived peptide AE36 (HER2:776–790). A phase I trial administering AE37 with the immunoadjuvant GM-CSF demonstrated the vaccine to be safe and capable of stimulating CD4+helper T-cells with HER2−specific anti-tumor activity. Here we present an update of our prospective, randomized, single-blinded, phase II trial of the AE37 vaccine for the prevention of breast cancer recurrence in disease-free, high risk patients.
Methods After completion of standard therapy, disease-free, node positive or high risk node negative breast cancer patients were randomized to receive either AE37+GM-CSF (vaccine) or GM-CSF alone (control) in six monthly intradermal inoculations. Patients were enrolled with any level of HER2 expression, (IHC 1+ 2+ or 3+). Specific immunologic responses to both AE36 and AE37 were evaluated in all patients at pre-determined intervals: before (RO), mid-series (R3), upon completion (R6), and at six (RC6) and 12 (RC12) months after completion of the vaccine series. In vitro responses were measured using the [3H]-thymidine incorporation assay and in vivo responses using delayed-type hypersensitivity (DTH) reactions. The trial's primary endpoint is disease recurrence.
Results To date, 215 patients have enrolled (vaccine=92, control=123). 99% of local and systemic toxicities were ≤grade 2 or less. There were no grade 4–5 local or systemic toxicities and no difference between toxicity profiles of vaccine and control groups. Vaccine patients exhibited a statistically significant increase from baseline in AE36 and AE37 proliferative responses at each time point, including maintenance of this response up to 12 months post-vaccination (AE36 (cpm): R0=0, R3=1335, R6=1242, RC6=1586, RC12=1360; AE37: R0=0, R3=2859, R6=2300, RC6=3235, RC12=3279, p&lt;0.001) while there have been no proliferative changes for control patients (AE36: R0=91, R3=95, R6=97, RC6=126, RC12=48; AE37: R0=291, R3=399, R6=319, RC6=103, RC12=0). Vaccine patients also had statistically significant increases in DTH reactions to both AE36 and AE37 (AE36 (mm): R0=0, R6=15, RC6=15, RC12=15; AE37: R0=0, R6=24, RC6=17, RC12=20 p=&lt;0.001) while controls had no response (AE36: R0, R6, RC6, RC12=0; AE37: R0, R6, RC6, RC12=0). With a median follow up of 17 months, breast cancer recurrences were reduced by 42% in vaccine patients compared to control patients (7.6% vs. 13.2%, p=0.15). In an analysis of patients with low HER2 expression (IHC 1 or 2+), vaccine patients experienced a 49% reduction in recurrence compared to controls (9.5% vs. 18.6%, p=0.16) with no reduction seen in HER2 over-expressing patients (6.0% vs. 7.9%, p=0.49).
Conclusions The AE37 vaccine is safe and well tolerated with only mild toxicity, which is attributable to the GM-CSF immunoadjuvant. The AE37 vaccine elicits strong peptide specific in-vivo and ex-vivo immune responses, which are maintained for 12 months after completion of the vaccine series. While the number of recurrences are still low, the recurrence rate appears to decrease in vaccinated patients. Administration of the AE37 vaccine may reduce the risk of breast cancer recurrence with the greatest benefit in patients with low levels of HER2 expression.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-13-01.