Abstract C35: Response of colorectal cancer cells to combination of EGFR mAbs with oxaliplatin is determined by the sequence of administration.

Abstract

Abstract Monoclonal antibodies (mAb) targeting EGFR (epidermal growth factor receptor), cetuximab (Erbitux) and panitumumab (Vectibix), have been approved for the therapy of metastatic colorectal cancer (mCRC). However, the majority of the patients are primarily resistant to EGFR mAbs or become resistant during the treatment. While activating mutations in KRAS have been reported to confer resistance to EGFR mAbs, some recent randomised controlled trials with EGFR mAbs combined to oxaliplatin-based regimens have failed to demonstrate clinical effect even in patients with KRAS wild-type mCRC. We have addressed the effects of EGFR mAbs on the growth of KRAS wild-type and KRAS mutant CRC cell lines in the absence and presence of oxaliplatin. Our observations indicate that while the KRAS mutant genotype is predictive for resistance to single agent EGFR mAbs, the combination of EGFR mAb plus oxaliplatin is not superior to oxaliplatin alone regardless of the KRAS status. However, sequential administration of oxaliplatin prior to EGFR mAb results in a clear additive effect whereas a sequence of EGFR mAb prior to oxaliplatin antagonizes the effect of oxaliplatin. The opposing effects of the two different sequences seem to be independent on both KRAS and BRAF mutation status. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C35.