Epidermal growth factor receptor T790M mutation as a prognostic factor in EGFR-mutant non-small cell lung cancer patients that acquired resistance to EGFR tyrosine kinase inhibitors.

Hai Jiang,Guangzhi Ma,Jing Zhang,Nannan Zhang,Qinghua Zhou,Liyuan Yin,Wen Li

doi:10.18632/oncotarget.19681

Hai Jiang, Guangzhi Ma + Show 5 more

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https://doi.org/10.18632/oncotarget.19681

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Journal: Oncotarget	Publication Date: Jul 29, 2017
Citations: 8	License type: cc-by

Affiliation: West China Hospital of Sichuan University

Abstract

Epidermal growth factor receptor (EGFR) T790M mutation accounted for over half of drug resistance cases in EGFR-mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) and led to different outcomes. This study aimed to assess the prognostic role of T790M in NSCLC patients treated with EGFR-TKIs that developed drug resistance. Eligible literatures were reviewed from various databases and a meta-analysis was performed to evaluate the prognostic role of T790M mutation in EGFR-TKIs treated patients that went progression. Three studies containing 192 patients were included in the meta-analysis. The pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were 0.66 (95% CI 0.49–0.89, P = 0.007) and 0.53 (95% CI 0.35–0.79, P = 0.002) respectively. Subgroups analyses were also performed on OS and PFS according to patients’ districts, gender and histological type. In conclusion, T790M as a common mutation to cause drug-resistance in EGFR-TKIs treated NSCLC patients may be a favorable prognostic factor on OS and PFS both. Further studies are necessary to demonstrate the prognostic role of secondary T790M in NSCLC patients.

Highlights

Lung cancer is and continues to be the leading cause of cancer death globally, accounting for over 1.1 million cancer deaths annually [1, 2]
Eligible literatures were reviewed from various databases and a meta-analysis was performed to evaluate the prognostic role of T790M mutation in Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) treated patients that went progression
Some studies indicated that patients with advanced non-small cell lung cancer (NSCLC) who underwent EGFR-TKIs had more favorable outcomes as first-line treatment compared to chemotherapy [9,10,11]

Summary

Introduction

Lung cancer is and continues to be the leading cause of cancer death globally, accounting for over 1.1 million cancer deaths annually [1, 2]. Some studies indicated that patients with advanced NSCLC who underwent EGFR-TKIs had more favorable outcomes as first-line treatment compared to chemotherapy [9,10,11]. T790M in exon 20 of EGFR gene was first reported by Kobayashi et al, and proved to cause drug resistance in NSCLC patients treated with EGFR-TKIs [16]. Since T790M mutation could cause drug resistance in NSCLC patients treated with EGFR TKIs, the existence of such mutation should associate with patients’ prognosis. Oxnard et al first reported that patients with acquired T790M mutation had relatively favorable outcomes compared to those without in NSCLC patient that developed EGFR-TKIs resistance [20]. According to a study conducted by Zheng et al, T790M led to poorer outcomes on OS in advanced NSCLC EGFR-TKIs treated patients that underwent progression [22]

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