Targeting Uncommon EGFR Mutations in Advanced NSCLC

Balazs Halmos, MD


August 11, 2022

Approximately 10%-20% of White patients and 50% of Asian patients with advanced nonsquamous, non–small cell lung cancer (NSCLC) harbor EGFR mutations. The introduction of first- and second-generation EGFR-targeted tyrosine kinase inhibitors (TKIs) has transformed the treatment of patients with EGFR-mutated tumors. And now a third-generation TKI, osimertinib, has become a preferred frontline option.

However, approximately 10%-15% of patients with EGFR-mutated tumors harbor uncommon EGFR mutations. Although some less common EGFR mutations, such as codons G719 and S768, have shown sensitivity to TKI therapy, others, such as exon 20 insertion mutations, have shown TKI resistance.

Dr Balazs Halmos of Montefiore Medical Center in Bronx, New York, reports on promising new molecules such as poziotinib and mobocertinib, which have shown early evidence of activity against tumors with certain uncommon EGFR mutations. Dr Halmos also discusses a breakthrough bispecific antibody, amivantamab, which may eventually be combined with TKIs in the treatment of all EGFR mutation–positive NSCLCs.


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