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

Updated: Jul 15, 2021
  • 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 mutations 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 and as category 2A with EGFR mutations such as exon 19 deletion or L858R discovered during first-line systemic therapy. For exon 20 insertion, amivantamab (Rybrevant) is indicated. [91]  

The presence of a KRAS mutation is prognostic of poor survival and has been associated with reduced responsiveness to EGFR TKI therapy.(REF – 91) KRAS G12C accounts for approximately 50% of KRAS mutations in NSCLC and is present in approximately 14% of patients with NSCLC. [142]  For patients with KRAS G12C–mutated locally advanced or metastatic NSCLC who have received 1 or more prior systemic therapies, consider sotorasib (Lumakras). [91]  


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