Efficacy of Icotinib, an EGFR Tyrosine Kinase Inhibitor in Non-Small Cell Lung Cancer Patients with Exon 19 Deletion and Exon 21 L858R: A Retrospective Analysis in China

Pharmacology. 2021;106(11-12):658-666. doi: 10.1159/000519847. Epub 2021 Oct 21.

Abstract

Introduction: The effect of icotinib on non-small cell lung cancer (NSCLC) patients with EGFR exon 19 deletions (19-Del) or L858R point mutation in exon 21 (21-L858R) remains inconsistent. This study aimed to evaluate the efficacy and safety of icotinib in patients with advanced NSCLC harboring these 2 EGFR mutations.

Methods: We retrospectively assessed the clinical effects of first-line icotinib on advanced NSCLC patients with 2 classic EGFR mutations. Kinase activity assays were used to reaffirm the preclinical efficacy.

Results: Among 2,757 patients, 2,365 (86%) harbored 19-Del (1,346/2,757, 49%) or 21-L858R (1,019/2,757, 37%) mutation. Patients with 19-Del had a higher response rate (ORR; 67.8 vs. 62.1%; p = 0.0039) and disease control rate (98.5 vs. 97.2%; p = 0.0223) than those with 21-L858R mutation. The median progression-free survival (PFS) in the 19-Del group (22.3 months, 95% confidence interval [CI]: 21.3-23.4) was significantly longer than that in the 21-L858R group (20.4 months, 95% CI: 19.5-21.7) (p = 0.004). In multivariate analysis, mutation types, clinical stage, and smoking history were significant factors for PFS. Additionally, an in vitro study indicated the 50% inhibitory concentrations (IC50) of icotinib was lower for EGFR 19-Del than 21-L858R.

Conclusion: These results suggest that EGFR 19-Del confers superior PFS and response to the icotinib treatment compared to 21-L858R.

Keywords: Epidermal growth factor receptor; Exon 19 deletion; Icotinib; L858R point mutation in exon 21; Non-small cell lung cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • China
  • Crown Ethers / administration & dosage
  • Crown Ethers / adverse effects
  • Crown Ethers / therapeutic use*
  • Dose-Response Relationship, Drug
  • ErbB Receptors / genetics
  • Exons
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Progression-Free Survival
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / administration & dosage
  • Quinazolines / adverse effects
  • Quinazolines / therapeutic use*
  • Retrospective Studies
  • Smoking / epidemiology
  • Smoking / pathology

Substances

  • Antineoplastic Agents
  • Crown Ethers
  • Protein Kinase Inhibitors
  • Quinazolines
  • icotinib
  • EGFR protein, human
  • ErbB Receptors