Molecular analysis of the randomized phase II/III study of the anti-IGF-1R antibody dalotuzumab (MK-0646) in combination with cetuximab (Cx) and irinotecan (Ir) in the treatment of chemorefractory KRAS wild-type metastatic colorectal cancer (mCRC)

3531 Background: Previously reported results of this randomized study demonstrated that the addition of dalotuzumab (Dz) worsened the PFS and OS of chemofractory mCRC patients receiving Cx and Ir (Watkins et al; ASCO 2011). Comprehensive molecular analysis has been undertaken retrospectively to identify possible predictors of Cx resistance and Dz response. Methods: Quantitative RT-PCR for IGF-1, IGF-2, immunohistochemistry for IGF-1R and microarray expression profiling was conducted on archival tumor tissue. All patients had received Cx and Ir with either placebo (n=107), weekly Dz (n=112), or 2 weekly Dz (n=110). Results: Data from 292 and 206 patients was successfully obtained by RT-PCR or microarray respectively. Within the placebo arm, high IGF-1 expression was found to be associated with resistance to Cx (IGF-1-/IGF-1+; PFS 6.7/3.7 months, OS 15.5/9.6 months). High IGF-1 expression was associated with benefit from the addition of weekly Dz (placebo/weekly Dz; PFS 3.7/5.7 months, OS 9.6/18.2 months). ...