Activation of DR leading to apoptosis was also investigated in a randomized phase II trial using an agonistic monoclonal antibody (moAb) against DR5 (conatumumab) combined with FOLFIRI versus FOLFIRI in the second-line setting and the experimental arm showed a trend toward an improved PFS with a better ORR. 114 Anti-EGFR-based treatments for RAS MT mCRC It is knowledge that RAS mutations cause primary and secondary resistance to anti-EGFR moABs in mCRC. 4 , 14 , 55 However, different RAS codon mutations have been hypothesized to underlie discrepancies in the anti-EGFR response.
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