Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Title: Lung-molGPA in EGFR-mutated Adenocarcinoma: Prognostic Implications of Molecular Subtypes and Targeted Therapies

Version 1 : Received: 29 July 2020 / Approved: 31 July 2020 / Online: 31 July 2020 (09:30:53 CEST)

How to cite: Kuan, F.-C.; Shi, C.-S.; Yang, W.-H.; Lin, M.-H.; Lai, H.-Y.; Huang, C.-C.; Yang, C.-T. Title: Lung-molGPA in EGFR-mutated Adenocarcinoma: Prognostic Implications of Molecular Subtypes and Targeted Therapies. Preprints 2020, 2020070739. https://doi.org/10.20944/preprints202007.0739.v1 Kuan, F.-C.; Shi, C.-S.; Yang, W.-H.; Lin, M.-H.; Lai, H.-Y.; Huang, C.-C.; Yang, C.-T. Title: Lung-molGPA in EGFR-mutated Adenocarcinoma: Prognostic Implications of Molecular Subtypes and Targeted Therapies. Preprints 2020, 2020070739. https://doi.org/10.20944/preprints202007.0739.v1

Abstract

EGFR mutations are heterogenous but all carry the same weighting 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. 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). A total of 256 patients were included with a median overall survival (OS) of 17.2 months. In multivariate analysis of OS, only age (70 versus <70 years, HR:1.71, 95% CI:1.25-2.35, p<0.001), KPS (<70 versus 70, 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, 18.8 vs 12.4 vs 12.1 months, p=0.021). In conclusion, different molecular subtypes treated with frontline TKIs have different prognostic implications in the Lung-molGPA. Further prospective studies are warranted to validate these findings.

Keywords

Lung-molGPA; exon 19 deletion; Leu858Arg; rare mutation; prognostic implication

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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