KRAS Gene Copy Number as a Negative Predictive Biomarker for the Treatment of Metastatic Rectal Cancer With Cetuximab: A Case Report

BackgroundClose to one third of colorectal cancer (CRC) patients are diagnosed with metastatic CRC (mCRC). Patients with wild-type RAS and BRAF usually receive anti-EGFR monoclonal antibody therapy containing cetuximab. Overall, 30-50% of mCRC patients are reported to harbor RAS mutations, and RAS mutation status should be assessed when considering EGFR inhibitor treatment according to mCRC biomarker guidelines. Of note, 0.67-2% of patients with CRC harbored a KRAS amplification. Here we reported a case of advanced rectal cancer with wild-type RAS and BRAF in a male patient who harbored a KRAS amplification during anti-EGFR treatment. Case PresentationA 46-year-old man was diagnosed with rectal adenocarcinoma with liver metastases (cT3NxM1a, stage IVA). After receiving first-line irinotecan- fluorouracil chemotherapy (FOLFIRI) plus cetuximab, second-line capecitabine- oxaliplatin chemotherapy (XELOX) plus bevacizumab, and third-line regorafenib, he rechallenged FOLFIRI and cetuximab for seven cycles, achieving a prolonged survival of at least 5 months. The KRAS copy number of circulating tumor DNA (ctDNA) was assessed during treatment. Notably, apart from serum carbohydrate antigen 199 (CA199) and carcinoembryonic antigen (CEA), the change of plasm Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) copy number appeared to strongly correlate with treatment response. ConclusionOur findings suggest that the dynamic change of KRAS copy number on ctDNA during treatment might be a negative predictive biomarker. Additionally, RAS and BRAF wild-type mCRC patients who are resistant to first-line FOLFIRI plus cetuximab therapy may respond well to the FOLFIRI plus cetuximab rechallenged strategy.

Automated summary

We reported a case of a male patient with advanced rectal cancer who harbored a KRAS amplification during anti-EGFR treatment. The dynamic change of KRAS copy number on ctDNA appeared to strongly correlate with treatment response, suggesting it as a potential negative predictive biomarker. Additionally, RAS and BRAF wild-type mCRC patients who are resistant to first-line FOLFIRI plus cetuximab therapy may respond well to the FOLFIRI plus cetuximab rechallenged strategy.