Use of wild-type (wt) KRAS, BRAF, and PIK3CA, combined with KRAS mutations (mut) in codon 13 and RNA expression level of amphiregulin (AREG) and epiregulin (EREG), to predict cetuximab (CE) response with high accuracy in colorectal cancer of all four Dukes' stages.

517 Background: wt KRASand wt BRAF are established clinical markers to predict response to CE in patients (pts) with mCRC. Some pts with KRASmut in codon 13 respond to CE, while the majority of them do not. Recently, it was shown that pts with CRC of Duke C and wt KRASand wt BRAF do not benefit from CE added to FOLFOX(ASCO 2011 abstr 3607). In addition, data indicated that AREG and EREG RNA expression is also correlated with CE response. We established a panel of 133 xenograft models from primary tumor tissue of pts with CRC of all four Dukes stages and conducted a therapy experiment with CE (AACR '11, LB9086). Methods: mut status of KRAS(G12, G13, A146T); BRAF ( V600E) and PIK3CA (E542K, E545K, H1047R) was assessed in all xenografts by allele-specific RT-PCR. KRAScodon 61 was sequenced. AREG and EREG expression levels were analyzed by RT-PCR expression assays. Results: We observed response to CE (treated to control ratio < 20%) in 18/67 (27%) of the treated xenografts. The distribution of responder ...