Abstract
4556 Background: HER2 positivity is thought to be a negative prognostic factor in GC, correlating with poor survival rates. Reported HER2-positivity rates in GC have varied widely (6–35%). The ToGA trial is evaluating the addition of trastuzumab (Herceptin) to chemotherapy in HER2-positive advanced GC. It is the first randomised Phase III trial to provide prospective information on HER2-positivity rates in GC. Enrollment is complete, with 3,883 patients screened in 24 countries. The pathological features of GC and the relationship with HER2 positivity will be examined. Methods: Advanced GC tumour samples were centrally screened by immunohistochemistry (IHC; HercepTest) and fluorescence in situ hybridisation (FISH; PharmDx) in parallel. A HER2-scoring system modified from the protocol in breast cancer (BC) was used: a score of IHC 3+ and/or FISH positive was defined as HER2 positive. Results: Final data showed an overall HER2-positivity rate of 22.1% evaluated from 3807 patients. The HER2-positivity rate was similar between Europe (23.6%) and Asia (23.5%). HER2-positivity rates were higher in gastro-oesophageal junction (GEJ) than stomach cancer (33.2% vs 20.9%; p<0.001) and in intestinal than diffuse/mixed cancer (32.2% vs 6.1%/20.4%; p<0.001). This is reflected in above-average HER2-positivity rates in countries with the highest GEJ:stomach cancer ratios (France 0.56 [HER2 positivity 26.9%]; Germany 0.53 [23.7%]; UK 0.33 [25.8%]) and intestinal:diffuse cancer ratios (UK 3.4 [HER2 positivity 25.8%]; Australia 2.6 [32.8%]; Japan 2.8 [27.8%]). The modified HER2-scoring system showed concordance between IHC and FISH results of 87.5%. In BC most IHC 0/1 samples are FISH negative but, in ToGA, the frequency of IHC 0/1 samples testing FISH positive was almost as high as IHC 2/FISH-positive samples (23% vs 26%). Conclusions: The overall HER2-positivity rate in advanced GC in ToGA is 22.1%. Variations in tumour location and type mostly explain the difference in HER2-positivity rates between countries. Efficacy data will enable further evaluation of the clinical significance of HER2 IHC and FISH scoring patterns. [Table: see text]
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