e21621 Background: EGFR mutations are heterogenous but all carry the same weight in the Lung-molGPA. The aim of this study was to elucidate the different prognostic implications of molecular subtypes and frontline TKIs in EGFR-mutated lung adenocarcinoma with synchronous brain metastases (BM) using the Lung-molGPA. Methods: Medical records were searched in hospital databases from 2011 to 2015. Patients with EGFR-mutated adenocarcinoma and brain metastases who received TKIs were included. The Kaplan-Meier method was used to estimate survival, and multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results: A total of 256 patients were included with a median overall survival (OS) of 17.2months. Patients with Lung-molGPA scores of 1, 1.5-2.0, 2.5-3.0, and 3.5-4.0 had median OS of 5.9,11.5, 17.2, and 23.4months, respectively (p < 0.001). In multivariate analysis of OS, only age (³70 versus < 70 years, HR:1.71, 95% CI:1.25-2.35, p < 0.001), KPS ( < 70 versus ³70, HR:1.71, 95% CI:1.26-2.31, p < 0.001), and rare mutations (other versus exon 19 deletions, HR:1.78, 95% CI:1.04-3.05, p = 0.037) remained statistically significant. In patients with a Lung-molGPA score £2.5, EGFR molecular subtypes had different median OS (exon 19 deletions versus Leu858Arg versus other, 18.9vs 12.8vs 4.5months, p = 0.021) and prognostic implications (Leu858Arg versus exon 19 deletions, HR: 1.85, 95% CI: 1.20-2.84, p = 0.005; other versus exon 19 deletions, HR:2.18, 95% CI:1.11-4.26, p = 0.023). Conclusions: Different molecular subtypes treated with frontline TKIs have different prognostic implications in the Lung-molGPA. Further prospective studies are warranted to validate these findings.
Title: Lung-molGPA in EGFR-mutated Adenocarcinoma: Prognostic Implications of Molecular Subtypes and Targeted Therapies