Abstract
This pooled analysis aims at evaluating the diagnostic accuracy of circulating tumor (ct) DNA for the detection of EGFR-T790M mutation in NSCLC patients who progressed after EGFR-TKIs. Data from all published studies, reporting both sensitivity and specificity of plasma-based EGFR-T790M mutation testing by ctDNA were collected by searching in PubMed, Cochrane Library, American Society of Clinical Oncology, European Society of Medical Oncology and World Conference of Lung Cancer meeting proceedings. A total of twenty-one studies, with 1639 patients, were eligible. The pooled sensitivity of ctDNA analysis was 0.67 (95% CI: 0.64–0.70) and the pooled specificity was 0.80 (95% CI: 0.77–0.83). The pooled positive predictive value (PPV) was 0.85 (95% CI: 0.82–0.87) and the pooled negative predictive value (NPV) was 0.60 (95% CI: 0.56–0.63). The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 2.67 (95% CI: 1.86–3.82) and 0.46 (95% CI: 0.38–0.54), respectively. The pooled diagnostic odds ratio (DOR) was 7.27 (4.39–12.05) and the area under the curve (AUC) of the summary receiver operating characteristics (sROC) curve was 0.77. The ctDNA analysis represents a promising, non-invasive approach to detect and monitor the T790M mutation status in NSCLC patients. Development of standardized methodologies and clinical validation are recommended.
Highlights
This pooled analysis aims at evaluating the diagnostic accuracy of circulating tumor DNA for the detection of epidermal growth factor receptor (EGFR)-T790M mutation in non-small cell lung cancer (NSCLC) patients who progressed after EGFR-tyrosine kinase inhibitors (TKIs)
The methodological quality of each trial was assessed by QUADAS-2, showing that the overall quality of included studies was good (Fig. 7). This meta-analysis included twenty-one studies (1639 patients) investigating the diagnostic accuracy of EGFR-T790M mutation testing by ctDNA in patients with advanced NSCLC who progressed to prior EGFR-TKI
Oxnard et al have recently demonstrated that a subgroup of plasma T790M-positive patients receiving osimertinib in the AURA 1 study who were T790M-negative on tissue analysis had favorable clinical outcomes to T790M-positive patients on tumor tissue[17]
Summary
This pooled analysis aims at evaluating the diagnostic accuracy of circulating tumor (ct) DNA for the detection of EGFR-T790M mutation in NSCLC patients who progressed after EGFR-TKIs. Several randomized phase III trials[1,2,3,4,5,6,7,8] demonstrated a significant survival benefit of EGFR-tyrosine kinase inhibitors (TKIs) over platinum-chemotherapy for naïve patients with advanced non-small cell lung cancer (NSCLC) carrying exon 19 deletion or exon 21 L858R point mutation. These data led to the clinical approval of first and second-generation TKIs as new standard upfront therapy in about 40% of Asian and 12% of Caucasian “EGFR-positive” NSCLC patients[9]. The aim of this pooled analysis is to combine and analyze simultaneously all the studies comparing ctDNA to tumor tissues based T790M-genotyping in order to provide a more precise estimation of the diagnostic accuracy of ctDNA analysis in patients with EGFR-mutant advanced NSCLC
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