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