P2.14-57 Efficacy of 3rd Generation EGFR-TKIs After Failing First or Second Generation EGFR-TKIs in EGFR Mutation-Positive NSCLC (ROOT-EGFR)

Abstract

Over the past decade, treatment of EGFR mutation –positive NSCLC has been revolutionized with the development of next generation EGFR TKIs. Four epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), erlotinib, gefitinib, afatinib and osimertinib, are currently available in Korea. Recent trials have compared the available and emerging EGFR TKIs head to head. The highly anticipated findings of the phase III FLAURA trial showed a nearly doubling of PFS with frontline osimertinib, a third-generation TKI, versus erlotinib or gefitinib. The optimal sequence of EGFR TKIs is still controversial. And many countries 3rd generation EGFR TKI is not readily available. The purpose of this study is to analyze the efficacy in patients who received first-line gefitinib, erlotinib, or afatinib and followed by 3rd generation EGFR-TKIs. This non-interventional observational study through big data analysis will retrospectively collect de-identified patient data from clinical data warehouse (CDW) using a unique algorithm with Standard Query Language (SQL) called ROOT project. Over 10 years, 2,358 patients were diagnosed recurrent or metastatic non-small cell lung cancer and received 1st or 2nd generation EGFR TKIs at Samsung Medical Center. 72.9% (1720/2358) of EGFR mutation-positive NSCLC patients received 1st or 2nd generation EGFR-TKIs as first line palliative chemotherapy. In total population, 30.8% (727/2358) patients received 3rd generation EGFR TKIs. Among them, patients who received 3rd generation EGFR TKI after 1st or 2nd generation EGF TKIs showed better overall survival (45.0 months (95% CI, 41.8-48.2). Among 1720 patients who received 1st or 2nd generation EGFR-TKIs as first line palliative chemotherapy, 313 patients received 3rd generation EGFR-TKIs as 2nd line chemotherapy and 200 patients received as more than 3rd line chemotherapy. However, there was no difference of overall survival between them (44.0 months vs 47.0months, p-value=0.104). This study was meaningful as a study of what can be the best sequence in EGFR-TKI treatment. Updated and detail clinical and exploratory biomarker outcome will be presented at the meeting.