What are options for targeted therapy in patients with non–small cell lung cancer (NSCLC) adenocarcinoma and endothelial growth factor receptor (EGFR) mutations?

Updated: Jun 05, 2020
  • Author: Winston W Tan, MD, FACP; Chief Editor: Nagla Abdel Karim, MD, PhD  more...
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Answer

EGFR testing that identifies sensitivity to EGFR-directed tyrosine kinase inhibitors (TKIs) include exon 19 deletions or the L858R point mutation. The T790M and exon 20 insertion have been associated with low response or acquired resistance to TKIs. In patients with adenocarcinomas that have EGFR mutations consistent with TKI sensitivity, options for single-agent targeted therapy without chemotherapy (first-, second-, or subsequent-line) include the following:

  • Osimertinib (Tagrisso)
  • Erlotinib (Tarceva)
  • Afatinib (Gilotrif)
  • Gefitinib (Iressa)
  • Dacomitinib (Vizimpro)

NCCN guidelines recommend osimertinib as the preferred category 1 option for first-line therapy in patients who have EGFR mutations documented before first-line chemotherapy. [93] Other EGFR-directed TKIs are also recommended as first-line agents include erlotinib, afatinib, gefitinib, or dacomitinib. Additional options include the following:

  • For tumors with EGFR T790M mutation, osimertinib (Tagrisso) is indicated.
  • The EGFR monoclonal antibody cetuximab (Erbitux) may be used in combination with chemotherapy.

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