Abstract
IntroductionMethods used for epidermal growth factor receptor (EGFR) mutation testing vary widely. The impact of detection methods on the rates of response to EGFR-tyrosine kinase inhibitors (TKIs) in EGFR-wild type (wt) lung adenocarcinoma patients is unknown.MethodsWe recruited the Group-I patients to evaluate the efficacy of erlotinib in patients with EGFR-wt lung adenocarcinoma by either direct sequencing (DS) or mutant type-specific sensitive (MtS) methods in six medical centers in Taiwan. Cross recheck of EGFR mutations was performed in patients who achieved objective response to erlotinib and had adequate specimens. The independent Group-II lung adenocarcinoma patients whose EGFR mutation status determined by DS were recruited to evaluate the potential limitations of three MtS methods.ResultsIn Group-I analysis, 38 of 261 EGFR-wt patients (14.6%) achieved partial response to erlotinib treatment. Nineteen patients (50.0%) had adequate specimens for cross recheck of EGFR mutations and 10 of them (52.6%) had changes in EGFR mutation status, 5 in 10 by DS and 5 in 9 by MtS methods originally. In Group-II analysis, 598 of 996 lung adenocarcinoma patients (60.0%) had detectable EGFR mutations. The accuracy rates of the three MtS methods, MALDI-TOF MS, Scorpions ARMS and Cobas, were 87.8%, 86.8% and 85.8%, respectively.ConclusionsA significant portion of the erlotinib responses in EGFR-wt lung adenocarcinoma patients were related to the limitations of detection methods, not only DS but also MtS methods with similar percentages. Prospective studies are needed to define the proper strategy for EGFR mutation testing.
Highlights
Methods used for epidermal growth factor receptor (EGFR) mutation testing vary widely
From August 2005 to March 2013, we evaluated the efficacy of erlotinib in lung adenocarcinoma patients (Group – I) with EGFR-wild type (EGFR-wt) status assessed by regular methods used in six participating medical centers in Taiwan (Taichung Veterans General Hospital, (TCVGH) Taipei Veterans General Hospital, Chang Gung Memorial Hospital (CGMH), Kaohsiung Medical University Hospital, National Taiwan University Hospital Yunlin Branch and Far Eastern Memorial Hospital)
There was no significant difference in progression-free survival (PFS) between patients with EGFR-wt tumors assessed by direct sequencing (DS) and by mutant type-specific sensitive (MtS) methods (2.0 vs. 1.9 months, P = 0.855) and similar survival periods were noted in overall survival (OS) analysis (8.3 vs. 10.9 months, P = 0.782)
Summary
Methods used for epidermal growth factor receptor (EGFR) mutation testing vary widely. The impact of detection methods on the rates of response to EGFR-tyrosine kinase inhibitors (TKIs) in EGFR-wild type (wt) lung adenocarcinoma patients is unknown. Epidermal growth factor receptor (EGFR)targeted therapy has emerged as a novel and effective strategy in lung cancer management with major benefits in patients with EGFR activating mutations. In front line and in subsequent therapy, EGFR-tyrosine kinase inhibitors (TKIs) in comparison with chemotherapy have demonstrated significantly higher response rate and longer progression-free survival (PFS) in patients with EGFR-mutant non-small cell lung cancer (NSCLC) [1]. Various EGFR mutation detection methods were used in studies regarding the efficacy of erlotinib in EGFR-wt NSCLC and their false negative rates have been suspected to be a possible reason for the responses to EGFR-TKIs in patients without detectable EGFR mutations [14,15]
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