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A. Winther Larsen
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-017 - Genetic Variations in the EGFR Gene Predicts Outcome in Advanced NSCLC Patients Treated with Erlotinib (ID 812)
09:30 - 09:30 | Author(s): A. Winther Larsen
- Abstract
Background:
Genetic variations in the epidermal growth factor receptor (EGFR) gene may alter protein expression or function and influence response to tyrosine kinase inhibitors. This study evaluates the role of genetic polymorphisms in the EGFR gene in advanced non-small cell lung cancer (NSCLC) patients treated with erlotinib. EGFR mutation status was known for all patients.
Methods:
Genotypes for -216G>T, -191C>A and 181946C>T in the EGFR gene were retrospectively evaluated by DNA sequencing and polymerase chain reaction in 354 Caucasian patients with advanced NSCLC. Hundred and seven of the patients had a somatic EGFR mutation, and all patients had been treated with erlotinib. Genotypes were correlated with clinical characteristics and outcome. A multivariate analysis was conducted adjusting for clinical relevant factors, including EGFR mutation status, using Cox proportional hazards model. A subgroup analysis was performed based on the EGFR mutation status.
Results:
Patients harboring at least one variant T allele (CT or TT) at position 181946 had a significantly longer median progression-free survival (PFS) (5.6 versus (vs.) 2.9 months; p =0.032) and overall survival (OS) (8.3 vs. 6.7 months; p=0.032) compared to patients with the CC genotype. The result remained significant in a multivariate analysis; PFS, adjusted hazard ratio (AHR)=0.73 (95% confidence interval (CI): 0.55-0.98); OS, AHR=0.72 (95%CI: 0.54-0.97). Patients carrying -216GT or TT genotypes showed a trend to a better clinical outcome compared to those with the GG genotype. The -216GT or TT and 181946CT or TT combined genotypes showed an even more pronounced association with clinical outcome compared to patients with the -216GG and 181946CC genotype (PFS, AHR=0.66 (95%CI: 0.44-0.98); OS, AHR=0.58 (95%CI: 0.38-0.87)). A subgroup analysis demonstrated that the association might be most relevant in EGFR mutation-positive patients; PFS, AHR=0.27 (95% CI: 0.11-0.68); OS, AHR=0.33 (95% CI: 0.13-0.83).
Conclusion:
A combination of 181946C>T and -216G>T polymorphisms in the EGFR gene seems to be a potential predictor of longer PFS and OS in advanced NSCLC patients treated with erlotinib; especially in EGFR mutation-positive patients. A prospective randomized study is wanted to confirm our data.
