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Interim Analysis of a Randomized Phase II Study of the Novel HER2/ Neu Peptide (GP2) Vaccine To Prevent Breast Cancer Recurrence: United States Military Cancer Institute Clinical Trials Group Study I-05.

2009; American Association for Cancer Research; Volume: 69; Issue: 24_Supplement Linguagem: Inglês

10.1158/0008-5472.sabcs-09-5110

1538-7445

Guy T. Clifton, Jarrod P. Holmes, Sonia A. Perez, D. Lorentz, K. Georgakopoulou, Linda C. Benavides, Jeremy D. Gates, Maj Elizabeth A. Mittendorf, Alexandros Ardavanis, Angelos D. Gritzapis, Sathibalan Ponniah, Michael Papamichail, George E. Peoples,

Monoclonal and Polyclonal Antibodies Research

Abstract BACKGROUND: HER2/neu-derived peptides that stimulate CD8+ T-lymphocytes are being evaluated in vaccine trials. We present results of a prospective, randomized, single-blinded phase II clinical trial of a HLA-A2/A3-restricted, HER2/neu peptide (GP2, HER2/neu 654-662) + GM-CSF immunoadjuvant vaccine versus GM-CSF alone in disease-free, high risk breast cancer (BCa) patients to prevent disease recurrence.METHODS: Disease-free, high risk BCa patients who have completed standard adjuvant therapy were enrolled and randomized to receive six monthly inoculations of either 500 mcg of GP2 with 125 mcg of GM-CSF (Peptide group; PG) or 125 mcg of GM-CSF alone (adjuvant group; AG). Toxicity was assessed after each inoculation. Immunologic response was monitored by measured delayed type hypersensitivity reactions (DTH) and an HLA-A2:Immunoglobulin dimer assay to detect GP2-specific CD8+ T-lymphocytes. Patients were monitored clinically, radiographically, and pathologically for recurrence.RESULTS: Thus far, 50 (27 PG, 23 AG) of the planned 200 patients have completed the primary series. The PG and AG have similar demographic/prognostic characteristics (Table 1). Toxicity profiles in the PG and AG were nearly identical with no grade 4-5 local toxicities and no grade 3-5 systemic toxicities in either arm. Median DTH reaction to GP2 increased significantly from pre-vaccination level after completion of the primary series (post-vaccination) in the PG group (1.0±0.8 cm to 18.0 ±3.1 cm; p<0.0001) and to a lesser extent in the AG group (0.0±1.0 cm to 0.5±3.3 cm; p<0.01). The post-vaccination DTH was significantly larger in the PG compared to the AG (18.0 ±3.1 cm vs 0.5±3.3 cm, p=0.002). All (27/27) PG patients displayed significant immunity (SI) by DTH (reaction larger than 1 cm) post-vaccination compared 45.5% (10/22) of AG patients. Of the 10 AG patients with post-vaccination SI, 50% (5/10) had pre-vaccination SI compared to just 16.6% (2/12) without SI post-vaccination (p=0.38). The % GP2-specific CD8+ lymphocytes significantly increased from baseline at 6 months after completion of the primary series in the PG (0.65±0.15 to 1.82± 0.23, p=0.002) and did not change significantly in the AG (1.08 ± 0.16 to 1.41 ± 0.49, p=0.45). At a median follow up of 17.9 months, the recurrence rate in the PG is 7.4% (2/27) compared to 13% (3/23) in the AG (p=0.65).CONCLUSIONS: The HER2/neu peptide GP2 is safe with the mild toxicities primarily due to the GM-CSF immunoadjuvant. GP2 + GM-CSF elicits a strong in vivo response, while GM-CSF alone may expand in vivo immune response in patients with pre-existing GP2-specific immunity. Additionally, GP2+ GM-CSF expands HER2/neu-specific CD8+ T-lymphocytes ex vivo. Additional study will be required to determine if there is a clinical benefit to GP2 vaccination.Table 1: Demographics PeptideAdjuvantp=N=2723 Age (median)52510.88Node Positive51.9%69.6%0.32Grade 351.9%56.5%1Tumor >= 2 cm66.7%52.2%0.45ER/PR negative40.7%43.5%0.92HER2 over-expressor59.3%47.8%0.60 Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5110.