Mutations in Circulating Tumor DNA and Clinical Outcomes of Rechallenge Treatment With Anti-EGFR Antibodies in Patients With Metastatic Colorectal Cancer.

Purpose: Several trials have evaluated the efficacy of rechallenge treatment with anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) in patients with metastatic colorectal cancer (mCRC). A recent trial indicated that status in circulating tumor DNA (ctDNA) may potentially predict patients with wild-type mCRC resistant to anti-EGFR mAb who would benefit from rechallenge treatment, and the findings should be further investigated.

Material And Methods: We enrolled patients whose plasma samples were collected in prospective phase II trials, the JACCRO CC-08 (n = 36) and CC-09 (n = 25), which evaluated rechallenge chemotherapy with anti-EGFR mAb for wild-type mCRC. in ctDNA was analyzed at the time points of baseline, 8 weeks, and progression using OncoBEAM RAS CRC kit.

Results: Sixteen patients were enrolled in this study, with a response rate of 0% and a disease control rate (DCR) of 62.5%. mutations were found at baseline in six patients. The DCR was 33% in patients with mutations in ctDNA, whereas it was 80% in patients without mutation at baseline. Patients with mutation at baseline had significantly shorter progression-free survival (PFS) and overall survival (OS) than those without mutation (median PFS, 2.3 4.7 months; hazard ratio [HR], 6.2; = .013; median OS, 3.8 16.0 months; HR, 12.4; = .0028). Six of 10 patients without mutation at baseline acquired mutations at progression. Postprogression survival after rechallenge treatment was numerically shorter in patients with mutation at progression.

Conclusion: status in ctDNA was significantly associated with clinical outcomes in patients with mCRC receiving rechallenge treatment with anti-EGFR mAb. These findings could support the clinical utility of OncoBEAM RAS CRC kits for anti-EGFR mAb rechallenge in wild-type mCRC.