P51.06 Outcomes of First-Line TKI Treated Advanced NSCLC with Distinct Types of EGFR Mutations: Brain Metastasis and de Novo T790M

Abstract

Listen

Translate article

The clinical features, survival outcomes and patterns of treatment failure of advanced non-small cell lung cancer (NSCLC) patients harboring distinct subtypes of EGFR mutations and receiving first-line EGFR tyrosine kinases inhibitor (TKIs) are not fully understood. Consecutive metastatic EGFR-mutant NSCLC patients receiving first-line EGFR-TKIs were enrolled and classified into two groups based on the EGFR mutation subtypes: common mutation (L858R or exon 19 deletion), uncommon mutation (other EGFR mutations). Of the 1081 patients included, 74 (6.8%) harbored uncommon mutations. The baseline characteristics were generally balanced between the two groups, except that bone metastasis developed less frequently in patients with uncommon mutations (p=0.02). No significant difference of survival outcomes was found between the two groups, except that among patients with baseline brain metastasis, the intracranial time to progression was significantly shorter in patients with uncommon mutations. Nine of the 17 patients with de novo T790M mutation received Osimertinib, whose overall survival tended to be longer than the remaining 8 patients without Osimertinib treatment (p=0.08), and those harboring common mutations and receiving second-line Osimertinib after developing acquired T790M mutation (n=116) (p=0.10). The patterns of treatment failure were generally consistent between the two groups, except that patients with uncommon mutations had higher risk developing progressive disease in the brain. First-line EGFR-TKIs seems to be less effective in controlling and preventing brain metastasis in patients with uncommon EGFR mutations and Osimertinib is associated with promising efficacy in patients with de novo T790M mutation, which warranted further validation