Use of genetic variants in immune response genes to predict clinical outcome in mCRC patients treated with cetuximab-based therapy.

Abstract

3567 Background: Cetuximab is a monoclonal antibody targeting the EGF receptor. One of its anti-tumor mechanisms is the stimulation of the immune system via ADCC (Antibody-Dependent-Cell mediated Cytotoxicity). Immune response through T-cell activation may also play a role in antitumor efficacy of chemotherapy. CTLA4, PDL1, IDO1 and CD24 are inhibitory co-receptors or ligands that may downregulate the immune system through suppression of T-cell response. We tested whether Germline polymorphisms in these genes are involved in the cetuximab dependent immune response pathway and thus predict outcome in mCRC patients treated with cetuximab. Methods: DNA was isolated from blood of 108 patients with mCRC treated with either irinotecan+cetuximab (n=73) or single agent cetuximab (n=35). Twelve prospectively functionally relevant SNPs; IDO1(rs9657182, rs3739319, rs1010866), PD1(rs2227981, rs7421861), PDL1(rs2297137, rs2297136, rs10122089, G>C), CTLA4(rs231777, rs231775), and CD24(rs8734) were analyzed by PCR-based direct sequencing and evaluated for association with tumor response, overall survival (OS), and progression free survival (PFS). Results: Results are attached. There were 65 men and 43 women with a median PFS of 3.7 (95%CI: 2.8, 4.6) months and a median OS of 10.5 (95%CI:7.7, 13.3) months. Median follow up was 16.3 (range:1.2, 42.4) months. Conclusions: Our results show that immune response related SNPs may predict efficacy of cetuximab treatment in patients with mCRC. To the best of our knowledge this is the first data linking PDL1(rs2297137) to cetuximab efficacy in mCRC patients. [Table: see text]