Table 2. Selected studies (n≥100) evaluating ctDNA to detect EGFR mutations in NSCLC.
| Study | Sample, n | Testing platform | EGFR alleles tested | Study objective | Concordance | Outcome |
|---|---|---|---|---|---|---|
| Jenkins et al., 2017 (16) | Plasma, 551 | cobas® EGFR Mutation Test v2.0, NGS | T790M | Percent agreement between plasma and tissue cobas test; ORR | Positive percent agreement: 61%; negative percent agreement: 79% |
ORR: 64% in T790M positive patients by both cobas tissue and plasma tests |
| Chen et al., 2017 (17) | Urine/plasma, 150 | ddPCR | L858R, L861Q, T790M | Comparison of tissue, plasma and urine to monitor NSCLC patients; OS | 88% between urine and tissue; 98% between urine and plasma |
T790M+ group had worse OS compared to T790M-(median OS 30 vs. 34 months) |
| Wu et al., 2017 (18) | Plasma/serum, 287 (serum), 334 (plasma) | Therascreen EGFR 29 Qiagen | 29 EGFR mutations | PFS; OS | EGFR mutation detection rates in cfDNA: 28.6% (serum); 60.5% (plasma) | Afatinib improved PFS vs. chemotherapy in cfDNA+ (HR: 0.25 to 0.35) and cfDNA-patients (HR, 0.12 to 0.46) |
| Reck et al., 2016 (19) | Plasma, 1,162 | Several different platforms used | Dependent on platform used | Concordance between plasma and tissue | 89% | Sensitivity: 46%; specificity: 97% |
| Zheng et al., 2016 (20) | Plasma, 117 | ddPCR | T790M | OS | – | T790M ctDNA positive group had significantly shorter OS than the negative group (median OS: 26.9 months vs. not achieved) |
| Thompson et al., 2016 (7) | Plasma, 102 | NGS | 70 gene platform | Feasibility of ctDNA to detect targetable mutations; OS | 79% | Higher cfDNA concentrations (>3 ng/ìL) was associated with a median OS of 24 vs. 46 months |
| Sequist et al., 2015 (21) | Plasma, 227 | BEAMing | T790M | ORR | 73% | Sensitivity: 80.7%; specificity: 34.3%; ORR was 48% in T790M+ patients, regardless of genotyping method |
| Weber et al., 2014 (22) | Plasma, 196 | cobas® EGFR Mutation Test | Exon 19 deletion, L858R | Concordance between plasma and tissue | 91.3% | Sensitivity: 91.3%; specificity: 60.7% |
| Jing et al., 2014 (23) | Plasma, 120 | High resolution melting analysis | Exon 19 deletion, L858R | Concordance between plasma and tissue | 85% | Sensitivity: 66.4%; specificity: 97.3% |
| Wang et al., 2014 (24) | Plasma, 134 | ARMS | Exon 19 deletion, L858R | Clinical significance of plasma EGFR mutations | 59% | Sensitivity: 22.1%; specificity: 97%; no difference in PFS or OS between patients with high and low levels of cfDNA |
| Douillard et al., 2014 (25) | Plasma, 652 | ARMS | Exon 19 deletion, L858R | Concordance between plasma and tissue; ORR; PFS | 94.3% | Sensitivity: 65.7%; specificity: 99.8%; no difference in ORR and PFR between mutation positive tumor or plasma |
| Zhao et al., 2013 (26) | Plasma, 111 | Mutant enriched PCR | Exon 19 deletion, L858R | Concordance between plasma and tissue | 71.2% | Sensitivity: 35.6%; specificity: 95.5% |
| Huang et al., 2012 (27) | Plasma, 822 | DHPLC | Exon 19 deletion, L858R | Concordance between plasma and tissue | 77% | Sensitivity: 63.5%; specificity: 84.6% |
| Bai et al., 2009 (28) | Plasma, 230 | DHPLC | Exon 19 deletion, L858R | Concordance between plasma and tissue; PFS | 74% | Sensitivity: 81.8%; specificity: 89.5%; patients with plasma EGFR mutations had a longer PFS than those without |
ORR, objective response rate; PFS, progression free survival; OS, overall survival; DHPLC, denaturing high-performance liquid chromatography; NSCLC, non-small cell lung cancer; EGFR, epidermal growth