EGFR mutation genotypes affect efficacy and resistance mechanisms of osimertinib in T790M-positive NSCLC patients

Translational Lung Cancer Research
Qiufan ZhengLi Zhang

Abstract

Osimertinib is a potent third-generation EGFR tyrosine kinase inhibitor (TKI) with robust activity in advanced EGFR-mutant non-small cell lung cancer (NSCLC), including those with T790M resistance mutation. However, a broad interpatient variability was observed. This study aimed to evaluate whether EGFR-mutant genotypes affect the clinical outcomes and resistance mechanisms in T790M-positive NSCLC patients receiving osimertinib therapy. All NSCLC patients treated with osimertinib in our institute were screened. We included those with known EGFR-mutant genotypes and T790M positivity. Clinical outcomes including objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), and overall survival (OS), were evaluated and compared between different EGFR genotypes. Patients with next-generation sequencing testing or tumor rebiopsy after osimertinib treatment were analyzed for resistance mechanisms. ORR, CBR, PFS, and OS were all non-significantly different among patients harboring EGFR exon 19 deletion (19Del, n=136), L858R (n=93), and uncommon mutations (n=6). However, a subset of tumors with deletion starting at E746 (ΔE746, n=98), but not non-ΔE746 tumors (n=38), had better clinical outcomes than L858...Continue Reading

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