Prospective analysis of the early modulation of plasma amphiregulin (AR) during treatment with cetuximab and irinotecan in irinotecan-refractory metastatic colorectal cancer (mCRC) patients (pts).

3602 Background: The potential role of AR tissue levels in the prediction of benefit from anti-EGFRs in mCRC pts was suggested by retrospective series. Preclinical and preliminary clinical experiences showed a modulation of plasma EGFR ligands during the treatment with cetuximab. Previous data by our group evidenced that a significant increase of plasma AR occurred one hour after the administration of cetuximab and higher increases were associated with worse clinical outcome in KRAS and BRAFwt irinotecan-refractory mCRC pts receiving cetuximab and irinotecan. Methods: We designed a prospective confirmatory study in the same setting of mCRC pts. To detect a HR for PFS of 2.3 for pts with high AR levels one hour after the administration of cetuximab (1hr-AR) compared to those with low levels, with two-sided a=0.05 and b=0.2, 45 events were required. The median value was adopted as cut-off. Plasma AR levels were assessed by means of validated ELISA kits. Results: Forty-nine KRAS and BRAFwt pts were included....