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].