Loss of RAS Mutations in Liquid Biopsies of Patients With Multi-Treated Metastatic Colorectal Cancer

Area of Science:

• Oncology
• Molecular Diagnostics
• Genetics

Background:

• Liquid biopsy (LB) offers non-invasive tumor heterogeneity assessment.
• RAS mutations (RAS-mut) are key in resistance to anti-epidermal growth factor receptor (EGFR) inhibitors.
• Serial monitoring of RAS-mut via LB can inform treatment strategies.

Purpose of the Study:

• To evaluate the prognostic value of loss of RAS mutations (NeoRAS-wt) detected by LB during metastatic colorectal cancer (mCRC) treatment.
• To assess the impact of NeoRAS-wt on survival outcomes in mCRC patients.

Main Methods:

• Retrospective study of mCRC patients (Jan 2018 - Dec 2021).
• RAS mutation status assessed in tissue biopsy at diagnosis and via LB during treatment.
• Analysis of overall survival (OS) and risk of death based on NeoRAS-wt detection.

Main Results:

• NeoRAS-wt was detected in 33.3% of 39 RAS-mut mCRC patients.
• Patients with NeoRAS-wt showed a median OS of 20 months vs. 9 months for persistent RAS-mut (P=.08).
• NeoRAS-wt predicted survival (HR=0.29; P=.007), improving median OS by 11 months and reducing death risk by 71%.

Conclusions:

• LB-based monitoring of clonal evolution in mCRC is valuable.
• Detecting NeoRAS-wt in advanced mCRC may identify patients eligible for further anti-EGFR Mabs therapy.
• This approach may offer an additional treatment line for selected mCRC patients.