A Trial Protocol of Precision Medicine for Patients with RAS Wild Metastatic Colorectal Cancer Using Liquid Biopsy...

Area of Science:

• Oncology
• Molecular Diagnostics
• Genomics

Background:

• Metastatic colorectal cancer (mCRC) patients without RAS mutations benefit from anti-epidermal growth factor receptor (EGFR) therapy, but responses can be inconsistent.
• Tumor molecular profiles can change during treatment, leading to resistance.
• Liquid biopsy via circulating tumor DNA (ctDNA) offers a non-invasive method to track molecular heterogeneity and real-time tumor changes.

Purpose of the Study:

• To evaluate the predictive value of ctDNA genomic mutations for primary and acquired resistance to anti-EGFR therapy in mCRC.
• To assess the utility of liquid biopsy in understanding treatment response in mCRC patients.

Main Methods:

• Prospective, multicenter observational study of mCRC patients with wild-type tissue RAS receiving first-line cytotoxic agents and anti-EGFR antibodies.
• ctDNA analysis using Droplet Digital PCR for mutations (RAS, BRAF, PIK3CA, EGFR) at baseline and every 3 months.
• Target sample size of 100 patients; primary endpoint is response rate in patients without baseline ctDNA RAS mutation.

Main Results:

• This section is to be filled once the study is completed and results are available.
• The study is designed to identify correlations between specific ctDNA mutations and treatment outcomes.
• Analysis will focus on response rates and resistance patterns based on ctDNA profiles.

Conclusions:

• The study aims to clarify the predictive role of baseline ctDNA RAS mutations in anti-EGFR therapy response.
• It will determine the frequency of emerging RAS, BRAF, PIK3CA, and EGFR mutations in ctDNA.
• The research will associate these emerging mutations with secondary resistance to anti-EGFR therapy in first-line mCRC treatment.