Targeted sequencing of patients with acquired resistance to third-generation EGFR tyrosine kinase inhibitors (TKIs) for EGFR T790M-mutant non-small cell lung cancer (NSCLC) revealed that resistance is associated with diverse pathways. The retrospective study looked at the genomic landscape of 113 specimens taken from patients with EGFR-mutant disease who had been previously treated with olmutinib or osimertinib.
Approximately 40% of patients had a disappearance of EGFR T790M. Of these, 59% had been treated with osimertinib and 21% with olmutinib. According to the researchers, those patients who lost the T790M mutation were more likely to show EGFR-independent pathways (small cell transformation; PIK3CA, PTEN, and BRAF mutation; FGFR1, MET, and HGF amplification; and CDKN2A deletion) as a secondary resistance mechanism.
Results suggest that there is a difference in the nature of resistance acquired after treatment with third-generation EGFR-TKIs, although not statistically significant according to the specific drug used. Read more.