Relationship of efficacy with KRAS status (wild type versus mutant) in patients with irinotecan-refractory metastatic colorectal cancer (mCRC), treated with irinotecan (q2w) and escalating doses of cetuximab (q1w): The EVEREST experience (preliminary data).

4001 Background: We previously demonstrated in the EVEREST trial that, in pts with mCRC after failure of irinotecan-based therapy, the efficacy could be improved by escalating the dose of cetuximab in combination with standard-regimen irinotecan (180 mg/m q2w) compared with standard-dose cetuximab for pts with grade 0/1 skin reactions. It has been suggested that KRAS mutation status may be a predictor for tumor response to anti-EGFR treatment. The question remains of whether dose escalation is also able to induce response in pts with mutated KRAS.,Pts with grade 0/1 skin reactions after 22 days of treatment with irinotecan and standard-dose cetuximab were randomized to receive standard dose (250 mg/m) (Arm A) or escalated (up to 500 mg/m) (Arm B) doses of cetuximab. Archived tissue from 77 of 89 randomized pts was analyzed for KRAS mutation status. Efficacy parameters were determined and compared with the outcome of KRAS mutation analysis.,In Arm A, 45 pts were randomized: 19 pts (42%) were KRAS wt, 19 pts (42%) were KRAS mt, and 7 pts (16%) were non-evaluable for the preliminary analysis. In Arm B, 44 pts were randomized and the figures were 28 (64%), 11 (25%), and 5 (11%), respectively. Updated data including PFS and additional correlations of KRAS status with ligands and mRNA predictive signatures will be presented.,These data suggest that patients with KRAS wt achieve considerable benefit from irinotecan plus cetuximab treatment. Patients with KRAS mt did not profit from irinotecan plus cetuximab treatment and cetuximab dose escalation did not increase responses in these patients. [Table: see text] [Table: see text].