1369P EGFR T790M ctDNA abundance and TP53 co-mutation by next generation sequencing predicted clinical outcomes of osimertinib in non-small cell lung cancer patients from a real-world study

Abstract

Osimertinib, the third-generation EGFR TKI, has been approved for non-small cell lung cancer (NSCLC) patients with EGFR T790M mutation after acquired resistance to the first-or second-generation of EGFR TKIs. However, the factors affecting the degree and duration of response to osimertinib is elusive. In this study, we aim to investigate the factors related to T790M abundance in ctDNA by next generation sequencing (NGS), and to analyze the association between the efficacy of osimertinib and T790M abundance in ctDNA. The study compromised 23 advanced EGFR T790M-mutated NSCLC patients which was detected by NGS after acquired resistance to the first-generation EGFR TKIs. The association between EGFR T790M abundance in ctDNA and clinicalpathological characteristics was performed by student t test or one-way ANOVA. Osimertinib outcomes were evaluated by osimertinib-related progression-free survival (PFS). The survival curves were calculated by the Kaplan-Meier method and analyzed by the log-rank test. Prior icotinib treatment led to the highest T790M abundance, compared with gefitinib and erlotinib. Older patients (The mPFS were 8.00±0.00 and 14.00±2.91months for patients older and younger than 68 years old, HR=0.15, 95%CI: 0.03-0.87, log-rank P=0.034), high T790M abundance (The mPFS were 9.00±1.48 and 25.00±0.00months for ctDNA T790M <4.2% and ≥4.2%, HR=0.17, 95%CI: 0.02-1.38, log-rank P=0.049) and prior icotinib (mPFS for patients who took gefinitb, erlotinib and icotinib were 14.00±7.33, 8.00±2.96 and 23.00±0.00months, HR=0.77, 95%CI: 0.43-1.39, log-rank P=0.014) were associated with improved osimertinib-related PFS. TP53 was the most common co-occurring mutations and led to shorter osimertinib-related PFS (mPFS for patients with or without TP53 co-mutation were 8.00±1.02 and 15.00±4.43months, HR=4.40, 95%CI: 0.82-23.49, log-rank P=0.042). T790M mutation abundance in ctDNA by NGS may be a novel method to predict the response and duration of osimertinib in the first-generation EGFR TKIs-resistant, T790M-mutated advanced NSCLC.