EGFR-Mutated Lung Cancers Resistant to Osimertinib through EGFRC797S Respond to First-Generation Reversible EGFR Inhibitors but Eventually Acquire EGFRT790M/C797S in Preclinical Models and Clinical Samples

Osimertinib is approved for advanced EGFR-mutated NSCLC, and identification of on-target mechanisms of resistance (i.e., EGFRC797S) to this third-generation EGFR inhibitor are evolving. Whether durable control of subsequently osimertinib-resistant NSCLC with the EGFR-sensitizing mutation (SM)/C797S is possible with first-generation EGFR inhibitors (such as gefitinib or erlotinib) remains underreported, as does the resultant acquired resistance profile.