Use of RAS pathway activation or KRAS mutation status to predict cetuximab response in CRC patient-derived xenografts.

3544 Background: Cetuximab was approved for treating EGFR-expressing metastatic colorectal carcinoma (mCRC) without patient stratification. Subsequent retrospective clinical studies resulted in an exclusion criterion for patients with KRAS mutations at codons 12 and 13. However, only a fraction of patients with wtKRAS benefit from the treatment. Recent analyses indicated that patients with KRAS mutation at codon 13 can also benefit. We set out to investigate whether KRAS mutations, or any other factors, are good biomarkers for CRC-cetuximab therapy patient stratification. Methods: We have established patient derived xenografts (PDX) from treatment-naive Asian CRC patients to discover biomarker predictive of cetuximab response. We conducted a clinical trial style study (“patient avatar trial”) of cetuximab using a randomly selected cohort of 26 EGFR+ PDXs. The antitumor activities were analyzed against KRAS mutation status and a published expression-signature. Results: We identified 12/26 (~46%) as cetuxim...