Abstract 2070
Background
Non-small cell lung cancer (NSCLC) with activating EGFR mutations in exon 19 and 21 usually responds to EGFR tyrosine kinase inhibitors (TKI), but sometimes the responses can only be maintained for a few months. The underlying mechanisms of such short responses have not been fully elucidated.
Methods
The genomic profiles of sixteen short-term responders (SR) that had progression free survival (PFS) of less than 6 months on the first-generation EGFR TKI were interrogated, in comparison to twelve long-term responders (LR) that had more than 24 months of PFS. All patients were diagnosed with advanced lung adenocarcinoma and harbored EGFR 19del or L855R mutation before treatment. Paired tumor samples collected before treatment and after relapse (or at the last follow-up) were subjected to next-generation sequencing of 416 cancer-relevant genes.
Results
SR patients were significantly younger than LR patients (p < 0.001). 88% of SR patients have TP53 variations compared to 13% in LR patients (p < 0.001), and 37.5% SR patients carry EGFR amplification, which is much higher than LR patients (8%). In addition, 12 SR patients (75%) were identified with other potential primary resistance mechanisms in pre-treatment samples, including PTEN loss, BIM deletion polymorphism, amplifications of EGFR, ERBB2, MET, HRAS and AKT2. Comparatively, only 3 LR patients (25%) were detected with EGFR or AKT1 amplification that could possibly exert resistance.
Conclusions
The diversified pre-existing resistance mechanisms in SR patients revealed the complexity of defining treatment strategies even for EGFR sensitive mutations.
Clinical trial identification
Legal entity responsible for the study
Fan Yun.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
X. Tong, X. Wu, Y.W. Shao: Employee: Geneseeq Technology Inc. J. Yan: Employee: Nanjing Geneseeq Technology Inc. All other authors have declared no conflicts of interest.
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