Predictive impact of different exon 19 deletions in EGFR-mutant NSCLC treated with first-line TKIs.

Abstract

e20608 Background: Common Epidermal Growth Factor Receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) predict sensitivity to EGFR tyrosine-kinase inhibitors (TKIs), with exon 19 deletions being associated with better outcome when compared to L858R mutations. We aimed to investigate the impact of different exon 19 deletions on patient outcome in EGFR-mutant NSCLC treated with first-line TKIs. Methods: In this retrospective analysis we included 98 patients with metastatic NSCLC and EGFR exon 19 deletions, treated with first-line EGFR TKIs (gefitinib or afatinib) in 3 Italian centers between 2011 and 2016. The primary endpoint was overall survival (OS), the secondary endpoint progression free survival (PFS). Analyses were performed by grouping exon 19 deletions according to two different models: type of deletion (delE746-A750 vs other) and starting codon of deletion (E746 vs L747). Kaplan-Meier method, the log-rank test and multivariate Cox regression models were used to estimate survival outcomes. Median follow-up time was 40 months. Results: All groups resulted well balanced in terms of patients’ characteristics but the percentage of patients treated with gefitinib was significantly superior in E746 group compared to L747 (p = 0.02). In the whole cohort median OS was 24.6 months [95%CI 21.9 – 33.1] while median PFS was 13.7 months [95%CI 11.6 – 15.9]. When delE746-A750 (n = 60) was compared to the other deletions in exon 19 (n = 38), no differences were evidenced either in terms of OS (24.1 vs 26.0 months; HR 0.80 [95%CI 0.5 – 1.4]; p = 0.42) or PFS (13.9 vs. 12.8 months; HR 0.99 [95%CI 0.6 – 1.6]; p = 0.97). Similarly, no difference in OS or PFS emerged comparing E746 (n = 73) versus L747 group (n = 25) (OS:24.6 and 26.0 months, respectively, HR 0.79 [95%CI 0.4 – 1.4; p = 0.45; PFS 13.9 vs 12.9 months, respectively (HR 0.87 [95%CI 0.5 – 1.4] p = 0.57). On multivariate analysis including age, sex, smoking history, deletions (delE746-A750 vs others or E746 vs L747), presence of brain metastases at diagnosis or during TKI treatment, no variable resulted associated with longer OS or PFS. Conclusions: Different exon 19 deletions are equally sensitive to first-line EGFR TKIs in EGFR-mutant NSCLC.