P-87 A multi-institutional observational study evaluating the efficacy of anti-epidermal growth factor antibody re-challenge in tissue RAS/BRAF wild-type metastatic colorectal cancer

Re-challenge of epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) is a treatment option for tissue RAS wild-type (WT) metastatic colorectal cancer (mCRC) in salvage-line treatment. This multi-center study investigated the efficacy of anti-EGFR mAb re-challenge and clinicopathological factors associated with treatment efficacy of anti-EGFR mAb re-challenge that is still unclear in the clinical practice. 74 mCRC patients with tissue RAS/BRAF WT, who were refractory or intolerant to previous chemotherapies, including fluoropyrimidines, oxaliplatin, irinotecan and anti-EGFR mAbs and whose RAS status in ctDNA was examined after prior chemotherapies using ONCOBEAMTM RAC CRC, were enrolled in 4 institutions from June 2021 to December 2022. Furthermore, the relationship of ctDNA RAS status, anti-EGFR mAb free interval and best response in previous anti-EGFR mAb with efficacy of anti-EGFR mAb re-challenge were investigated in patients who underwent anti-EGFR mAb re-challenge. The incidence of ctDNA RAS WT mCRC was 59.5% (44/74). Most common RAS genes in ctDNA were detected in KRAS codon 61 (n = 17, 33%), followed by KRAS codon 12 (n = 14, 27%) and NRAS codon61 (n = 12, 24%), respectively. There were significant differences in frequency of ctDNA RAS WT, between resection of primary tumor (+) vs (-) (75.0% [33/44] vs 40.7% [11/27], P = 0.016), absence vs presence of liver metastasis (100% [17/17] vs 47.4% [27/57], P 119.1 ng/ml vs ≤, 32.4% [12/37] vs 86.5% [32/37], P 88.8 U/ml vs ≤, 37.8% [14/37] vs 81.1% [30/37], P 12months (n = 22) vs ≤ 12months (n = 12) ; P Log-rank = 0.91, HR, 0.95; 95% CI, 0.39-2.33). Re-challenge of anti-EGFR mAb may be effective for patients without RAS mutations detected in ctDNA and those showing response in previous anti-EGFR mAb.