Monitoring ctDNA RAS Mutational Status in Metastatic Colorectal Cancer: A Trial Protocol of RAS-trace and RAS-trace-2...

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Metastatic colorectal cancer (mCRC) treatment with anti-EGFR monoclonal antibodies (mAbs) requires consideration of spatial and temporal gene heterogeneities.
• Acquired RAS mutations and discrepancies between tissue and circulating tumor DNA (ctDNA) RAS status are observed during anti-EGFR mAb treatment.
• These molecular changes necessitate further investigation in mCRC.

Purpose of the Study:

• To clarify the spatial and temporal heterogeneities of RAS and BRAF genes in mCRC.
• To investigate the clinical significance of these heterogeneities.
• To optimize anti-EGFR mAb treatment strategies in mCRC based on molecular profiling.

Main Methods:

• Two observational studies (RAS-trace and RAS-trace-2) were initiated using next-generation sequencing from liquid biopsies.
• RAS-trace monitors ctDNA RAS/BRAF/PIK3CA status every 4-12 weeks in mCRC patients with RAS/BRAF wild-type (wt) tumor tissue.
• RAS-trace-2 compares anti-EGFR mAb efficacy in patients with ctDNA RAS/BRAF wt versus mutant status, with wt tumor tissue.

Main Results:

• The RAS-trace study has accrued 42 patients, focusing on the time to acquired RAS mutations.
• The RAS-trace-2 study aims to accrue 240 patients over 2 years to compare progression-free survival.
• Detailed results on mutation acquisition and treatment efficacy are pending patient accrual and analysis.

Conclusions:

• These studies will enhance understanding of RAS and BRAF gene heterogeneities in mCRC.
• Findings are expected to guide the optimization of anti-EGFR mAb treatment strategies.
• Personalized medicine approaches in mCRC can be improved through liquid biopsy-based molecular monitoring.