Purpose: The purpose of this meta-analysis was to explore the influences of pretreatment de novo and posttreatment-acquired epidermal growth factor receptor (EGFR ) T790M mutations in patients with advanced non-small cell lung cancer (NSCLC) who had received tyrosine kinase inhibitors (TKIs).
Methods: We searched PubMed, Embase, and the China National Knowledge Infrastructure database for eligible literature. Data were extracted to assess the hazard ratios (HRs) for progression-free survival (PFS), overall survival (OS), and post-progression survival (PPS) and the relative ratios (RRs) for objective response rate (ORR).
Results: This meta-analysis included 22 studies comprising 1,462 patients with NSCLC who harbored activating EGFR  mutations and were treated with EGFR-TKIs. Compared to pretreatment T790M mutation-negative NSCLC, pretreatment T790M mutation-positive NSCLC was associated with decreased PFS (HR 2.23, P <0.001) and OS (HR 1.55, P =0.003). A trend toward significance of worsening ORR (RR 0.86, P =0.051) was evident. The acquired T790M mutation was correlated with improved PFS (HR 0.75, P =0.006) and PPS (HR 0.57, P <0.001), compared to patients without the T790M mutation who progressed after EGFR-TKI treatment. There were no significant differences in OS or ORR between patients with acquired T790M mutation-positive and T790M mutation-negative NSCLC. However, in the tumor tissue rebiopsy subgroup, patients with acquired T790M mutation had improved OS (HR 0.60, P <0.001) compared to T790M mutation-negative patients. In the plasma ctDNA subgroup, acquired T790M mutation decreased the OS (HR 1.87, P <0.001).
Conclusion: Pretreatment T790M mutation was associated with worse PFS and OS in patients with advanced NSCLC treated with EGFR-TKIs, while acquired T790M mutation was associated with longer PFS and PPS than T790M mutation-negative NSCLC. The effects on OS were different between acquired T790M mutation detected from rebiopsy of tumor tissue and that detected from plasma ctDNA.
Keywords: epidermal growth factor receptor, T790M, non-small cell lung cancer, pretreatment, mutation