Abstract B43: A subset of gastric cancers with EGFR amplification and overexpression respond to cetuximab therapy.

Gastric carcinoma (GC) is a common cancer of high mortality and particularly prevalent in East Asia. There are only a few treatment options: surgery, chemotherapy, as well as Herceptin® for a small subset of patients with erbb2 amplification. Cetuximab has been approved for CRC (colorectal) and SCCHN, but not yet for gastric carcinoma. Cetuximab, combined with capecitabine/cisplatin, has recently been tested in Phase III clinical trial (EXPAND) in GC patients (1), but failed to demonstrate benefit over the existing chemotherapy (capecitabine/cisplatin). One of the reasons for the failure is only small subset of patients responding to cetuximab, which constitutes little effects on large trial populations, while the identity of the responders yet to be revealed. One of the keys to a successful search for effective treatment is the development of experimental model that truly mimics patient conditions. Patient derived xenograft (PDX or HuPrime®) is believed to best mimic human cancers (2). Recently, we have established a cohort of ∼70 GC xenograft (PDX) models from Asian and Caucasian patients. In the present study, we conducted a mouse clinical trial (MCT, or PDX trial) to test cetuximab in a cohort of GC-PDX, aiming at identifying those responsive to cetuximab. Interestingly, our trial result identified 4 of 20 (20%) GC-PDX responded to cetuximab. Genome-wide profiling and additional investigations revealed that high EGFR mRNA expression and immunohistochemistry score (3+) are associated with tumor growth inhibition. Furthermore, EGFR amplification were observed in 4/4 (50%) responders by DNAchip analysis or 2/4 confirmed with FISH analysis, with average copy number 5.8 and >15 respectively. Our data suggest that a GC subtype with EGFR amplification and overexpression benefit from cetuximab treatment. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B43. Citation Format: Lianhai Zhang, Jie Yang, Yiyou Chen, Jie Cai, Xiaoming Song, Xuesong Huang, Jianyun Deng, Dawei Chen, Mengmeng Yang, Shuangxi Li, Aiwen Wu, Ziyu Li, Zhongwu Li, Yiqian Liu, Jean-Pierre Wery, Henry Li, Jiafu Ji. A subset of gastric cancers with EGFR amplification and overexpression respond to cetuximab therapy. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B43.