java swnig 太极,Concurrent gene alterations with EGFR mutation and treatment efficacy of EGFR-TKIs in ...

Concurrent gene alterations with EGFR mutation and treatment efficacy of EGFR-TKIs in Chinese patients with non-small cell lung cancer

Wentao Hu1, Yahui Liu2, Jian Chen1

1Department of Thoracic Surgery, Ningbo First Hospital, Ningbo, Zhejiang 315000, P.R. China

2Key Laboratory of Ningbo, Ningbo First Hospital, Ningbo, Zhejiang 315000, P.R. China

Correspondence to: Yahui Liu, email: ningboxwk@http://www.doczj.com/doc/3ffafa5b178884868762caaedd3383c4ba4cb457.html

Keywords: epidermal growth factor receptor, tyrosine kinase inhibitor, non-small cell lung cancer, concurrent gene, efficacy Received: November 10, 2016 Accepted: January 11, 2017 Published: February 15, 2017

Copyright: Hu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Purpose: We investigated the frequency of concurrent genes in EGFR-mutant non-small cell lung cancer patients and determined its value in predicting the efficacy

of EGFR-TKIs treatment.

Methods: Three hundred and twenty patients, who harbored EGFR activating mutations and received EGFR-TKIs treatment, were examined for another eight genes

including KRAS, NRAS, PIK3CA, BRAF, and HER2 mutations and ALK, ROS1, and RET

fusion genes based on reverse transcription PCR. Progression-free survival and overall

survival with EGFR-TKIs treatment were evaluated using Kaplan-Meier methods and

compared between different patients using log-rank tests.

Results: Twenty-one (6.6%) of 320 EGFR mutant samples with additional gene alterations were identified. The most common concurrent gene was PIK3CA mutation

(n = 9), followed by EML4-ALK rearrangement (n = 6), HER2 mutation (n = 3), RET

rearrangement (n = 1), ROS1 rearrangement (n = 1) and KRAS mutation (n = 1).

Patients with single EGFR mutation had a significantly longer progression-free survival

than those with concurrent genes (10.9 vs. 6.0 months, P = 0.002). Among the 21

cases, patients with PIK3CA mutation had the longest median progression-free survival

(7.6 months), followed by ALK rearrangement (5.0 months) and other gene types (1.2

months). No overall survival difference was found between patients with single EGFR

mutation and concurrent gene alterations (21.0 vs.17.6 months, P = 0.17).

Conclusion: We demonstrated that concurrent gene alterations occurred in some patients with EGFR mutations. Concurrent gene alterations decreased the efficacy of

EGFR-TKIs.

INTRODUCTION

Epidermal growth factor receptor (EGFR) mutations occur in about 40% to 50% of lung adenocarcinoma patients of East Asian descent [1, 2]. The median progression-free survival (PFS) is approximately 9 to 13 months and the objective response rate of 60% to 70% in patients carrying EGFR mutations treated with EGFR-TKIs [3–6].

Drug resistance is a big issue for most patients with clinically evident non-small cell lung cancer (NSCLC). T790M mutation, MET amplification and PIK3CA mutations contributed to secondary resistance to EGFR-TKIs and several new drugs targeting resistance have emerged [7–12]. Primary resistance is another challenge in clinical practice, however, the mechanism is not well investigated currently. Coexistent genetic alterations in cancer-driving genes, i.e., KRAS mutations, PTEN loss and BIM polymorphisms were identified to be associated with primary resistance for EGFR-TKIs treatment [13–14]. But, most studies focused on concurrent ALK and EGFR mutations [15–16]. Other genes such as PIK3CA and HER2 were not well reported. The

http://www.doczj.com/doc/3ffafa5b178884868762caaedd3383c4ba4cb457.html/oncotarget/Oncotarget, 2017, Vol. 8, (No. 15), pp: 25046-25054

Research Paper