The role of T790M mutation in EGFR-TKI re-challenge for patients with EGFR-mutant advanced lung adenocarcinoma

Abstract

Epidermal growth factor receptor (EGFR) T790M mutation has shown to be associated with the clinical outcomes of patients after initial EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy in EGFR-mutant advanced non-small cell lung cancer (NSCLC). However, its predictive role in EGFR-TKI re-challenge remains unknown. The present study was aimed to explore the correlation between T790M mutation and any benefits from EGFR-TKI re-challenge. We retrospectively reviewed 922 consecutive patients with EGFR-mutant non-small cell lung cancer (NSCLC) patients administered with gefitinib/erlotinib at Guangdong General Hospital. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) were analyzed respectively. In total, 66 EGFR-mutant patients with stage IV adenocarcinoma were eligible, of whom 51 underwent re-biopsy upon initial progression. Among them, 18 (35.3%) harbored T790M mutation. No statistical significant differences were seen between T790M-positive and T790M-negative patients in PFS, OS, ORR or DCR. The median PFS, median OS, ORR, and DCR of the overall 66 patients were 2.0 months, 6.8 months, 6.1% and 39.4%, respectively. Good performance status (PS) was found to be independent favorable prognostic factor and long TKI-free interval to be associated with superior PFS. In conclusion, T790M mutation might not predict the clinical outcomes in first-generation EGFR-TKI re-challenge. Based on the poor efficacy from our data, re-challenge of first-generation EGFR-TKIs could not be recommended routinely, but for those with good PS and long TKI-free interval, it might be an alternative option.