Comparison of direct sequencing and amplification refractory mutation system for detecting epidermal growth factor receptor mutation in non-small-cell lung cancer patients: a systematic review and meta-analysis

Qi Feng, Zu-Yao Yang, Jia-Tong Zhang and Jin-Ling Tang _

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Oncotarget. 2017; 8:59552-59562. https://doi.org/10.18632/oncotarget.19110

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Qi Feng1,*, Zu-Yao Yang1,*, Jia-Tong Zhang1 and Jin-Ling Tang1

1 Division of Epidemiology, JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong

* These authors have contributed equally to this work

Correspondence to:

Jin-Ling Tang, email:

Keywords: epidermal growth factor receptor, direct sequencing, amplification refractory mutation system, non-small cell lung cancer, tyrosine kinase inhibitors

Received: January 17, 2017 Accepted: June 27, 2017 Published: July 08, 2017


Background: Direct sequencing and amplification refractory mutation system (ARMS) are commonly used to detect epidermal growth factor receptor (EGFR) mutation status in patients with non-small-cell lung cancer to inform the decision-making on tyrosine kinase inhibitors treatment. This study aimed to systematically compare the two methods in terms of the rate of detected mutations and the association of detected mutations with clinical outcomes.

Material and methods: PubMed, EMBASE, China National Knowledge Infrastructure (in Chinese) and Wanfang database (in Chinese) were searched to identify relevant studies. Meta-analyses of EGFR mutation rates, rate differences, and the associations of EGFR mutations with clinical outcomes of tyrosine kinase inhibitors treatment were conducted.

Results: Eight hundred and sixty-six records were retrieved and 26 studies with 3282 patients were included. The pooled rate of mutations detected by ARMS (41%, 95% confidence interval (CI) 35% to 47%) was significantly higher than that by direct sequencing (28%, 95%CI 22% to 34%), with a weighted rate difference of 11% (95%CI 8% to 13%). There was a consistent trend that the associations between ARMS-detected mutations and clinical outcomes were stronger than those between direct-sequencing-detected mutations and clinical outcomes (pooled risk ratio for objective response: 5.18 vs. 2.25; hazard ratio for progression-free survival: 0.30 vs. 0.42; hazard ratio for overall survival: 0.46 vs. 0.54).

Conclusions: More patients with EGFR mutations can be identified by ARMS than by direct sequencing, and those identified by ARMS seems to be able to benefit more from tyrosine kinase inhibitors than those identified by direct sequencing.

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