The Concomitant Egfr T790m/C797s In Trans And Cis In Three Osimertinib-Resistant Lung Adenocarcinoma Patients.

e20105 Background: EGFR C797S mutation is an important cause of Osimertinib resistance. Previous studies showed that patients harboring EGFR C797S in trans with T790M are sensitive to a combination of first- and third-generation EGFR tyrosine kinase inhibitors (TKI). However, patients harboring EGFR C797S in cis with T790M are resistant to combination therapy or each single reagent. Methods: We performed next-generation sequencing on peripheral blood samples from patients with advanced lung adenocarcinoma who had been undergoing targeted therapy. Total DNA was extracted from formalin-fixed, paraffin-embedded tissue sections and quantified. Targeted regions of 14 lung cancer-associated genes were amplified by PCR, barcoded and sequenced using an Illumina MiSeq 500 platform. Results: Among 6489 Lung adenocarcinoma patients sample, we identified concomitant trans and cis EGFR T790M/C797S in three patients with very poor prognosis. All three patients were sensitive to the first-generation EGFR TKI, and took Osimertinib when disease progressed. When resistant to Osimertinib, the patients went to genetic testing to find new target therapy. Patient No. 1 was a 66-year-old man with mutations of EGFR exon 19del (25.08%), EGFR T790M (10.08%) / C797S (5.37%) in trans and in cis, TP53 exon8 mutation (12.35%). This patient died 20 days after the genetic testing without any further treatment. Patient No. 2 was a 53-year-old woman who carried gene mutations including EGFR exon 19del (0.51%), EGFR T790M (0.57%) and C797S (0.47%) in trans and in cis. She was treated with the combination of first- and third-generation EGFR TKI, and disease progressed after 50 days. She died half months after the gene test. Patient No. 3 was a 63-year-old woman whose gene mutation included EGFR L858R (77.49%), EGFR T790M (40.94%) and EGFR C797S (5.46%) in trans and in cis, also combined with EGFR amplification. Treatment with vascular endothelial growth factor receptor (VEGFR) inhibitor Anlotinib was attempted, but the patient died within one month after the gene test. Conclusions: We firstly reported three cases with concomitant EGFR T790M/C797S in trans and EGFR T790M/C797S in cis mutation in the word. Physicians tried either the EGFR TKI inhibitor combination therapy or VEGFR inhibitor, but neither of them had an effect on these patients. All three patients had very poor prognosis and died within two months of the gene test, indicating that the concomitant of the cis and trans mutation could be a very important prognostic prediction factor.