Genomic Alterations (Ga) Predicted To Confer Lack Of Benefit From Trastuzumab In Advanced Esophagogastric Cancers (Egc): Analysis Of 527 Her2-Amplified (Her2amp) Cases.

44Background: The addition of trastuzumab to chemotherapy improves survival in first line treatment of advanced HER2 overexpressing EGC. However, the response rate is under 50% in this molecularly heterogeneous group of cancers. Genomic alterations (GA) associated with lack of benefit from trastuzumab are understudied. Methods: We prospectively analyzed clinical samples from patients with EGC using hybrid-capture based comprehensive genomic profiling (CGP). Pre-specified literature review was used to determine GA associated with de-novo trastuzumab resistance. Results: From 2,245 gastroesophageal junction (GEJ) adenocarcinomas and 1,883 gastric adenocarcinomas (GC) we identified 395 HER2-amplified GEJ (18%) and 132 HER2-amplified (HER2amp) GC (7.0%) cases. Median HER2 copy number was 19 in GEJ and 16 in GC samples. PIK3CA GA and METamp were observed in ~9% and ~5% of both HER2amp and non- HER2amp EGC cases; however, co-amplification of cell-cycle mediators CDK6 and CCCNE1 were each significantly enriched ...