EGFR Amplification and Sensitizing Mutations Correlate with Survival in Lung Adenocarcinoma Patients Treated with Erlotinib (MutP-CLICaP)

Target Oncol. 2018 Oct;13(5):621-629. doi: 10.1007/s11523-018-0594-x.

Abstract

Background: Non-small cell lung cancer (NSCLC) has a 5-year survival of 5-16%. Epidermal growth factor receptor (EGFR) mutations, in most cases, confer sensitivity to EGFR tyrosine kinase inhibitor (TKI) therapy. Nonetheless, it is still unclear why clinical outcomes vary among patients with identical EGFR mutations. The amplification of the EGFR gene (EGFRamp) may play a significant role.

Objective: Compare the complete (CR) and partial response (PR) rates, overall survival (OS), and progression-free survival (PFS) in Hispanic patients with lung adenocarcinoma treated with erlotinib with EGFR mutations (L858R or exon 19 deletion [Del19]) with and without concomitant EGFRamp.

Patients and methods: Seventy-two EGFR-positive lung adenocarcinoma patients of Hispanic origin, who underwent first-line treatment with erlotinib, were evaluated for EGFRamp by fluorescence in situ hybridization (FISH). The clinical outcomes were analyzed according to EGFR mutations and EGFRamp status.

Results: 30.6% of samples showed EGFRamp, more frequently present in patients with Del19 (p = 0.05). Patients with EGFRamp had a longer PFS (in months) [(28.5, 95% CI 22.3-34.6) vs. (11.0, 95% CI 8.2-16.7); p = 0.002] and OS [(37.8, 95% CI 30.9-44.7) vs. (27.1, 95% CI 12.8-41.3); p = 0.009] than those without. EGFRamp significantly influenced the response to erlotinib (p = 0.0001). EGFRamp+/Del19 had a longer OS, 37.8 (95% CI 31.0-44.6), compared to EGFRamp+/L8585R, 27.5 (95% CI 12.4-42.5) (p < 0.001) and longer PFS (p = 0.043).

Conclusion: Among Hispanic patients, EGFRamp was present in 30% of patients with EGFR mutations. EGFR mutations and EGFRamp are associated with better OS, PFS, CR, and PR to erlotinib and, hence, could aid in the correct selection of patients that benefit from EGFR TKI treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / drug therapy*
  • Adenocarcinoma of Lung / enzymology
  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • Erlotinib Hydrochloride / therapeutic use*
  • Female
  • Gene Amplification
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Survival Analysis
  • Young Adult

Substances

  • Antineoplastic Agents
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors