Mutation abundance affects the therapeutic efficacy of EGFR-TKI in patients with advanced lung adenocarcinoma: A retrospective analysis

Cancer Biol Ther. 2018 Aug 3;19(8):687-694. doi: 10.1080/15384047.2018.1450115. Epub 2018 Apr 13.

Abstract

Purpose: To investigate the influence of mutation abundance and sites of epidermal growth factor receptor (EGFR) on therapeutic efficacies of EGFR-tyrosine kinase inhibitor (EGFR-TKIs) treatments of patients with advanced non-small cell lung carcinoma (NSCLC).

Methods: EGFR mutational sites and mutation abundance were analyzed by amplification refractory mutation system (ARMS) in paraffin-embedded tissue sections taken from primary or metastatic tumors of 194 NSCLC patients.

Results: The median progression-free survival (PFS) time of the enrolled patients was 9.3 months (95% CI, 8.2-10.8 months). The PFS was significantly different with EGFR gene mutation abundance after EGFR-TKI therapy (P = 0.014). The median PFS was significantly longer when the cut-off value of EGFR mutation abundance of exon 19 or exon 21, and solely exon 19 was > 26.7% and 61.8%, respectively. For patients who received EGFR-TKI as first-line treatment, the median PFS was significantly longer in the high mutation abundance group than in the low mutation abundance group (12.7 vs 8.7 months, P = 0.002).

Conclusion: The PFS benefits were greater in patients with a higher abundance of exon 19 deletion mutations in the EGFR gene after EGFR-TKI treatment and first line EGFR-TKI treatment led to improved PFS in high mutation abundance patients.

Keywords: ARMS; EGFR; EGFR-TKI; lung adenocarcinoma; mutation abundance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / drug therapy*
  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • ErbB Receptors / genetics
  • Exons
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Proportional Hazards Models
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • ROC Curve
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • EGFR protein, human
  • ErbB Receptors