Clinical features associated with NeoRAS wild-type metastatic colorectal cancer A SCRUM-Japan GOZILA substudy

Area of Science:

• Oncology
• Molecular Diagnostics
• Genetics

Background:

• Metastatic colorectal cancer (mCRC) treatment response is influenced by RAS mutation (MT) status.
• Acquisition of wildtype RAS (NeoRAS WT) status after therapy is a newly recognized phenomenon.
• Understanding NeoRAS WT incidence and characteristics is crucial for treatment optimization.

Purpose of the Study:

• To determine the prevalence and clinicopathological features of NeoRAS WT mCRC.
• To investigate the association of NeoRAS WT with patient characteristics and treatment outcomes.
• To evaluate the efficacy of anti-EGFR monoclonal antibodies (mAbs) in NeoRAS WT patients.

Main Methods:

• Analysis of plasma circulating tumor DNA (ctDNA) using next-generation sequencing.
• Inclusion of mCRC patients from the GOZILA study with initial tissue RAS MT.
• Definition of NeoRAS WT as absence of detectable RAS MT in plasma ctDNA.

Main Results:

• NeoRAS WT prevalence was 19.0% in all eligible patients and 9.8% in those with detected plasma alterations.
• Absence of liver/lymph node metastasis and specific tissue RAS MTs (excluding KRAS exon 2) were associated with NeoRAS WT.
• Partial response (1/6) and stable disease ≥6 months (2/6) were observed in NeoRAS WT patients treated with anti-EGFR mAbs.

Conclusions:

• NeoRAS WT mCRC occurs at a clinically relevant frequency.
• Emergence of NeoRAS WT status warrants further investigation.
• Anti-EGFR mAb therapy shows potential efficacy in NeoRAS WT mCRC patients.