Abstract P1-02-07: Discordance for low and intermediate levels (1+ or 2+ by IHC) of HER2 protein expression in the phase III PRESENT trial

Abstract

Abstract Background Significant discordance has been described between different laboratories and between testing methodologies for HER2 overexpression and gene amplification. Concern has focused on missing patients who might benefit from treatment with HER2 targeted therapy. Concordance rates between local and central testing for tumors selected for HER2 0-2+ is not well described. We describe discordance rates between local and central testing performed to identify tumors with 1 and 2+ HER2 expression. Methods The PRESENT study is a multicenter, multinational, prospective, randomized, double-blind, controlled Phase 3 study assessing efficacy and safety of the peptide vaccine NeuVax, in HLA-A2 and/or A3 positive patients with early stage, node positive breast cancer expressing low and intermediate levels (1/2+ by IHC) of HER2 protein. PRESENT 2-step screening includes HLA testing followed by central lab confirmation of HER2 1 or 2+ expression using the DAKO HercepTest. Results 215 patients underwent central IHC testing for HER2. Discordance between local and central testing was seen in 54% (117/215); 34% (65/192) of those eligible by local results were ineligible on central testing, and 48% (11/23) of those not eligible by local results were eligible on central testing. Local testingCentral testing (IHC (%))IHC (n)01+2+3+0 (15)5 (33%)7 (47%3 (20%)—1+ (127)39 (31%)68 (53%)15 (12%)5 (4%)2+ (65)11 (17%)23 (35%)21 (32%)10 (16%)3+ (8)3 (38%)—1 (12%)4 (50%) Of those with 1 or 2+ local results, 8% (15/192) were found to be 3+ on central testing. Discordant rates varied by geographic location with higher rates seen in Eastern Europe and Russia. Conclusion Significant discordance exists between local and central laboratory test results for HER2 expression by IHC even at lower levels of expression, and current tests are defined by their ability to determine 3+ positivity. In order to improve accuracy of testing and to develop a companion diagnostic for NeuVax, the Leica Bond Oracle HER2 IHC System will be incorporated into future HER2 screening for the PRESENT trial. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-02-07.