NSCLC is a common cancer with one of the highest mortality numbers and few effective treatment options, except those with EGFR and ALK activating mutations. Cetuximab has been approved for CRC and H&N, but not yet for NSCLC. In this study, we set out to explore potential clinical utilities by testing cetuximab in a large cohort of patient derived xenograft (PDX) models (over established 60 models).

Among the 12 NSCLC models tested so far, 5 out of 12 were found to be sensitive (42%), with all of which have wild-type KRAS and EGFR except for 1 model that carries an EGFR exon-20 a short in-frame insertion. These data suggest that cetuximab could potentially benefit a subgroup of patients, although it remains to be seen whether cetuximab can offer additional benefit besides standard chemotherapy regimens through combinational therapies. Among the 7 resistant models, two of them have L858R mutation in EGFR, a known driver mutation for non-smoking Asian female patients who are sensitive to gefitinib treatment. This data suggests that although both cetuximab and gefitinib can block EGFR signaling, the mechanism of action may also play an important role in tumor response to drugs. Analysis of genomic analysis did not reveal obvious relationship between cetuximab sensitivity and EGFR expression level, nor EGFR copy number. This could be attributed the relative small cohort size so far.

Although the current study suggests that EGFR L858R mutation might be negatively correlated with response to cetuximab, additional studies with more PDX models are needed to further substantiate this observation, and for uncovering other biomarkers which could potentially predict patient populations who can benefit from cetuximab treatment.

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 B36.