Optimizing the sequencing of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). Review uri icon

Overview

abstract

  • Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 80-85% of cases. Epidermal growth factor receptor (EGFR) mutations are observed in approximately 40% and 20% of patients with NSCLC in Asian and non-Asian populations, respectively. First-generation (gefitinib, erlotinib) and second-generation (afatinib, dacomitinib) EGFR-tyrosine kinase inhibitors (TKIs) have been standard-of-care (SoC) first-line treatment for patients with sensitizing EGFR mutation positive advanced NSCLC following Phase III trials versus platinum-based doublet chemotherapy. However, most patients treated with first-line first- or second-generation EGFR-TKIs develop resistance. Osimertinib, a third-generation, central nervous system active EGFR-TKI which potently and selectively inhibits both EGFR-TKI sensitizing (EGFRm) and the most common EGFR T790 M resistance mutations, has shown superior efficacy versus first-generation EGFR-TKIs (gefitinib / erlotinib). Osimertinib is now a treatment option for patients with advanced NSCLC harboring EGFRm in the first-line setting, and treatment of choice for patients with T790 M positive NSCLC following disease progression on first-line EGFR-TKIs. The second-generation EGFR-TKI dacomitinib has also recently been approved for the first-line treatment of EGFRm positive metastatic NSCLC. There remains a need to determine appropriate sequencing of EGFR-TKIs in this setting, including EGFR-TKIs as monotherapy or in combination with other TKIs / signaling pathway inhibitors. This review considers the evolving role of sequencing treatments to maximize benefits for patients with EGFRm positive advanced NSCLC.

publication date

  • September 23, 2019

Research

keywords

  • Carcinoma, Non-Small-Cell Lung
  • DNA Mutational Analysis
  • High-Throughput Nucleotide Sequencing
  • Lung Neoplasms
  • Molecular Targeted Therapy
  • Mutation
  • Protein Kinase Inhibitors

Identity

PubMed Central ID

  • PMC7478849

Scopus Document Identifier

  • 85072630364

Digital Object Identifier (DOI)

  • 10.1016/j.lungcan.2019.09.017

PubMed ID

  • 31568888

Additional Document Info

volume

  • 137