The predicting role of circulating tumor DNA landscape in gastric cancer patients treated with immune checkpoint inhibitors

Mol Cancer. 2020 Oct 30;19(1):154. doi: 10.1186/s12943-020-01274-7.

Abstract

A more common and noninvasive predicting biomarker for programmed cell death 1 (PD-1) antibody remains to be explored. We assessed 46 patients with advanced gastric cancer who received PD-1 antibody immunotherapy and 425-genes next-generation sequencing (NGS) testing. Patients who had a > 25% decline in maximal somatic variant allelic frequency (maxVAF) had a longer progression free survival (PFS) and higher response rate than those who did not (7.3 months vs 3.6 months, p = 0.0011; 53.3% vs 13.3%, p = 0.06). The median PFS of patients with undetectable and detectable post-treatment circulating tumor DNA (ctDNA) was 7.4 months vs. 4.9 months (p = 0.025). Mutation status of TGFBR2, RHOA, and PREX2 in baseline ctDNA influenced the PFS of immunotherapy (p < 0.05). Patients with alterations in CEBPA, FGFR4, MET or KMT2B (p = 0.09) gene had greater likelihood of immune-related adverse events (irAEs). ctDNA can serve as a potential biomarker of the response to immunotherapy in advanced gastric cancers, and its potential role in predicting irAEs worth further exploration.

Keywords: Advanced; Biomarkers; Circulating tumor DNA; Gastrointestinal cancer; Immune checkpoint inhibitors.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Circulating Tumor DNA / blood
  • Circulating Tumor DNA / genetics*
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Male
  • Prognosis
  • Stomach Neoplasms / blood
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology*
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Circulating Tumor DNA
  • Immune Checkpoint Inhibitors