Patients harboring uncommon EGFR exon 19delins variants of advanced non-small-cell lung cancer and response to osimertinib: A multi-center retrospective study

e21184 Background: This study aims to investigate the efficacy of different EGFR inhibitors therapy in patients with advanced non-small-cell lung cancer (NSCLC) harboring atypical EGFR exon 19delins variants. Methods: Targeted sequencing database of 1426 treatment-naive patients with advanced NSCLC were retrospectively screened for EGFR exon 19 deletion (19del) variants in a multi-center study from January 2017 to January 2022, and 34 patients with uncommon EGFR exon 19 deletion-insertions (19delins) were included. The response rate, and progression-free survival (PFS) were analyzed according to the radiographic images. Results: We identified 3 previously unreported uncommon EGFR exon 19delins variants. Among the 34 patients who had uncommon EGFR19delins, 24 patients received first-generation, and 10 patients received third-generation as front-line EGFR TKI therapy, the median progression-free survival (mPFS) was significantly longer for patients who received first-generation than those with third-generation (19.1 months vs 6.9 months; HR: 0.18, 95% CI: 0.062-0.507; p < 0.001). At progression, EGFR T790M was the main acquired mechanism of resistance (8/14; 57.2%). There were 22 patients who received osimertinib therapy, the overall ORR and DCR were 54.5% and 81.8%, respectively, and the overall mPFS was 6.9 months. But no significant difference was observed in mPFS between first-line osimertinib and second-line osimertinib therapy (6.9 months vs. 3.8 months; p = 0.206). Conclusions: The uncommon EGFR exon 19delins variants of advanced NSCLC have longer mPFS for the first-generation compared with the third-generation as front-line EGFR TKI therapy, and respond poor to third-generation EGFR inhibitors, regardless of whether osimertinib was used as first-line or second-line therapy. Patients with uncommon EGFR exon 19delins may be a biomarker of poor efficacy with the third-generation EGFR TKI therapy.