Meta-analysis of the impact of de novo and acquired EGFR T790M mutations on the prognosis of patients with non-small cell lung cancer receiving EGFR-TKIs

Abstract

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.