HER-2 as a potential target for rectal cancer treatment: Positivity rate in patients of the CAO/ARO/AIO-94 and -04 trial.

Abstract

585 Background: Members of the EGFR family are established targets for specific therapy approaches in a variety of malignancies. Especially HER-2 has been targeted for more than a decade in breast cancer and more recently in gastric cancer and adenocarcinomas of the gastroesophageal junction. Applying the HER-2 scoring algorithm established in gastric cancer we here investigated HER-2 expression in rectal cancer using FFPE tumor samples from both large trials of the German Rectal Cancer Study Group (GRCSG)-(CAO/ARO/AIO-94 and -04). Methods: Overall, FFPE samples from 839 patients from 63 sites were available. All patients received standardized multidisciplinary treatment according to protocols of the phase-III-trials. 104 patients were treated by primary tumor resection followed by adjuvant CRT, all other patients (n=547) had preoperative CRT either with concomitant 5-FU mono therapy (n=329, 60.1%) or a combination of 5-FU and oxaliplatin (n=218, 39.9%). The HER-2-status was determined in resection specimens using immunohistochemistry scoring and S-ISH-amplification detection. Tumors with IHC 3+ or S-ISH ratios of ≥2.2 were classified HER-2-positive; these results were correlated with clinicopathological parameters (e.g., resection status, nodal-status ((y)pN)), time to recurrence (TTR) and cancer specific survival (CSS). Results: Positive HER-2-status was found in 13.8% of resected specimens. Positivity rate in primary resection specimens was 11.5% (n=12), while after preoperative CRT 13.2% (n=78 ) patients showed a HER-2 positive tumor; 13.1% (n=43) after 5-FU mono and 13.3% (n=35) after combination of 5-FU and oxaliplatin. There was no prognostic difference according to the HER-2 status regarding TTR (p=0.90) and CSS (p=0.68) overall. However in the 5-FU mono subgroup the HER-2 expression was of prognostic relevance as measured by CSS (p=0.034). Conclusions: Analysis of 839 patients from the GRCSG validated a relevant HER-2 amplification of 13.8% in samples of rectal adenocarcinoma. Besides its potential as an independent predictor of survival HER-2 may represent a promising target for innovative therapies and should be further assessed.