A man with recurrent lung adenocarcinoma harboring an EGFR exon 19 deletion received erlotinib for 10 months following curative surgery and adjuvant chemotherapy. However, he switched to osimertinib after repeat biopsy showed EGFR exon 19 deletion and T790M mutation leading to erlotinib resistance. His disease progressed after 15 months and repeat biopsy showed SCLC. Next-generation sequencing of peripheral blood detected EGFR exon 19 deletion, T790M mutation, cis-C797S mutation, and RB1 inactivation.

A 62-year-old woman with no history of smoking came into the clinic with pleural effusion (PE) in May 2013; stage IV lung adenocarcinoma…subsequent first-generation EGFR TKI treatments for EGFR exon 19 deletion…After 8 months of progression-free survival (PFS), the patient experienced development of a new lesion...Genetic testing of circulating tumor DNA from the PE revealed a newly acquired C797S mutation in cis with T790M...A combination of brigatinib (90 mg daily) and cetuximab (600 mg monthly, administered intravenously) has been administered since July 2017 (see Fig. 1A). The patient experienced significant improvement in her fatigue and dyspnea within 1 month...

We describe herein a patient whose tumor acquired an EGFR C797S mutation after treatment with a third-generation EGFR TKI. The acquired EGFR C797S should confer resistance to all third-generation EGFR TKIs...

To test whether DBZ resensitized EGFRC797S mutant human lung adenocarcinoma cells to osimertinib in vivo, we grafted PC9GROR cells subcutaneously in mice, and 2 weeks later, we treated them with DBZ and/or osimertinib for 3 weeks…Osimertinib alone had no significant effect on growth of PC9GROR cell xenografts...