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Comparison of direct sequencing and amplification refractory mutation system for detecting epidermal growth factor
Qi Feng1, Zu-Yao Yang1, Jia-Tong Zhang1
1Division of Epidemiology, JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
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.
Insights
Amplification refractory mutation system (ARMS) detects more epidermal growth factor receptor (EGFR) mutations than direct sequencing in non-small-cell lung cancer patients. ARMS-identified mutations show stronger associations with tyrosine kinase inhibitor treatment benefits.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Epidermal growth factor receptor (EGFR) mutation status is crucial for guiding tyrosine kinase inhibitor (TKI) treatment in non-small-cell lung cancer (NSCLC).
- Direct sequencing and amplification refractory mutation system (ARMS) are common methods for EGFR mutation detection.
- Comparing the efficacy of these diagnostic methods is essential for optimizing patient care.
Purpose of the Study:
- To systematically compare direct sequencing and ARMS for EGFR mutation detection in NSCLC patients.
- To evaluate the differences in mutation detection rates between the two methods.
- To assess the association of mutations detected by each method with clinical outcomes of TKI therapy.
Main Methods:
- A systematic literature search was conducted across PubMed, EMBASE, CNKI, and Wanfang databases.
- Meta-analyses were performed on EGFR mutation rates, rate differences, and associations with TKI treatment outcomes.
- Data from 26 studies including 3282 patients were analyzed.
Main Results:
- ARMS detected significantly more EGFR mutations (41%) compared to direct sequencing (28%), with a weighted rate difference of 11%.
- Mutations identified by ARMS showed stronger associations with improved objective response (RR 5.18 vs. 2.25), progression-free survival (HR 0.30 vs. 0.42), and overall survival (HR 0.46 vs. 0.54) compared to direct sequencing.
- A consistent trend indicated superior clinical outcome correlations with ARMS-detected mutations.
Conclusions:
- ARMS identifies a greater proportion of patients with EGFR mutations than direct sequencing.
- Patients with EGFR mutations identified by ARMS appear to derive greater clinical benefit from TKIs.
- ARMS may be a more sensitive method for selecting NSCLC patients for TKI therapy.
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