Thyroid transcription factor 1 (TTF-1) and overall survival in wild type EGFR patients treated with erlotinib.

Abstract

e19113 Background: TTF-1 is a transcription factor involved in regulating epithelial to mesenchymal transition. TTF-1 has a favorable prognosis in early stage lung adenocarcinoma, although it’s prognostic value in erlotinib treated patients remains unknown (Somaiah ASCO 2011). The goal of this study was to validate the relationship between TTF-1 expression and clinical outcomes in wild-type (WT) stage IV non-small cell lung cancer (NSCLC) patients (pts) treated with erlotinib. Methods: Pts that received erlotinib were retrospectively analyzed by IHC for TTF-1 expression (positive = greater than 5% of tumor cells with moderate (2+) or strong (3+) nuclear staining). Pts’ tumors were considered WT if no mutations were detected in Exon 19 or L858R (Exon 21) using single-strand conformation polymorphism and sequence-specific polymerase chain reaction (PCR). Log Rank was used to correlate TTF-1 positivity with outcomes. Results: 216 pts were analyzed. EGFR activating gene mutations were found in 11.6% of cases. TTF-1 positivity was strongly correlated with the presence of an activating EGFR mutation (p=.0006, negative predictive value=97.7%). Of WT pts: median age was 65, 61% female, 15% never smokers. TTF-1 was positive in 8% of squamous cell and 71% of adenocarcinoma pts. In EGFR WT pts, the median progression free survival (PFS) in TTF-1 positive and negative pts was 2.1 vs. 1.6 months respectively, p=.255. TTF-1 strongly correlated with prolonged overall survival (OS) on erlotinib therapy in WT pts (6.2 vs. 3.2 months, log rank p=.004). After excluding for squamous cell histology, in TTF-1 positive EGFR WT pts there was still a highly significant correlation with prolonged OS on erlotinib (6.2 vs. 2.8 months, p=.001) and a trend toward prolonged PFS (2.2 vs. 1.4 months, p=.05). Conclusions: TTF-1 is related to the presence of exon 19 and 21 EGFR mutations in this group of NSCLC pts, and, similar to early stage lung cancer, TTF-1 appears to be at least a prognostic indicator for OS in stage IV WT EGFR NSCLC pts treated with erlotinib. Exploration of the potential predictive value of this readily available marker should be considered in pts with EGFR WT tumors treated with erlotinib.