Monitoring of RAS mutant clones in plasma of patients with RAS mutant metastatic colorectal cancer

Clin Transl Oncol. 2022 Jun;24(6):1209-1214. doi: 10.1007/s12094-021-02767-7. Epub 2022 Jan 7.

Abstract

Purpose: Some patients with histologically confirmed primary mCRC and mutated RAS reported undetectable RAS mutant clones in plasma after receiving anti-VEGF treatment. The aim was to prospectively assess it with its potential therapeutic implications.

Methods: RAS mutant genes in solid biopsy (before first-line treatment: FOLFOX/CAPOX + bevacizumab) were compared in liquid biopsy (before second-line treatment: panitumumab + FOLFIRI), using Idylla™ system. Discordant results between solid/liquid biopsies were assessed by the next-generation sequencing (NGS) test (solid/liquid biopsies).

Results: Twenty-three patients were assessed (seven had RAS mutant discrepancies between solid/liquid biopsies). The NGS test confirmed that 3/23 (13%) patients had undetectable RAS mutant clones in liquid biopsy and 3/23 (13%) presented discrepancies in solid biopsy (Idylla™ system vs. NGS test).

Conclusion: Thirteen percentage of patients had undetectable RAS mutant clones in liquid biopsy after first-line treatment. However, some discrepancies between solid and liquid biopsies have been observed. These results suggest a need to improve accuracy of RAS analyses, especially in solid biopsies.

Keywords: Circulating tumor DNA; EGFR inhibitors; Liquid biopsy; Metastatic colorectal cancer; RAS mutant.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Clone Cells / pathology
  • Colonic Neoplasms* / drug therapy
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • Fluorouracil / therapeutic use
  • Humans
  • Mutation
  • Panitumumab / therapeutic use

Substances

  • Panitumumab
  • Fluorouracil