Table 1. Clinical studies examining EGFR mutations in cfDNA.
| First author | Name of the study | Population | No | Technique used | Results | Reference |
|---|---|---|---|---|---|---|
| Rosell | NEJM | EGFR mutant | 164 | Del 19: length analysis with PNA; L858R: PCR TaqMan assay with PNA | (I) EGFR mutations detected in 59.1% of samples at baseline; (II) L858R mutation in cfDNA related with shorter PFS |
(26) |
| Rosell | EURTAC | EGFR mutant | 109 | Del 19: length analysis with PNA; L858R: PCR TaqMan assay with PNA | (I) EGFR mutations detected in 53.2% of samples at baseline; (II) EGFR mutations in cfDNA related with shorter PFS |
(27) |
| Karachaliou | EURTAC | EGFR mutant | 97 | PCR TaqMan assay with PNA | EGFR mutations detected in 78% of samples at baseline | (11) |
| Mayo-de-las-Casas | Prospective screening study | Advanced NSCLC | 1,033 | PCR TaqMan assay with PNA | EGFR mutations detected in 11% of samples at presentation | (28) |
| Douillard | IFUM | Advanced NSCLC | 652 | TheraScreen EGFR RGQ PCR Kit | EGFR mutations detected in 65.7% of samples at presentation (99.8% specificity) | (29) |
| Wu | LUX-Lung 3/6 | EGFR mutant | 661 (LUX-Lung 3, 287; LUX-Lung 6, 334) | TheraScreen EGFR RGQ PCR Kit | Overall concordance: 28.6% (LUX-Lung 3) and 60.5% (LUX-Lung 6) | (30) |
| Mok | FASTACT-2 | Advanced NSCLC | 241 | Cobas test | (I) 75% sensitivity, 95% specificity and 88% concordance; (II) predictive role of EGFR mutations dynamic changes in cfDNA |
(31) |
| Wu | ENSURE | Advanced NSCLC | 517 | cobas EGFR Mutation Test v2 | (I) 76.7% sensitivity and 98.2% specificity; (II) FDA approval of the test |
(32,33) |
| Mok | AURA3 | EGFR T790M-positive NSCLC | 399 | cobas EGFR Mutation Test v2 | (I)4 6.57% sensitivity and 71.83% specificity; (II) PFS with osimertinib was similar regardless of selection by tissue or plasma T790M-positive status |
(34,35) |
| Oxnard | AURA | EGFR mutant progressing to EGFR TKI | 216 | Beaming | EGFR T790M: 70.3% sensitivity, 69% specificity | (36) |
| Sacher | NCT02279004 | Advanced NSCLC | 180 | ddPCR | (I) EGFR exon 19 deletions: 82% sensitivity, 100% specificity; (II) EGFR L858R: 74% sensitivity, 100% specificity; (III) EGFR T790M: 77% sensitivity, 79% specificity; (IV) KRAS: 64% sensitivity, 100% specificity |
(37) |
| Reck | ASSESS | Advanced NSCLC | 1,311 (1,288 eligible) | Therascreen EGFR RGQ PCR kit, Roche cobas EGFR Mutation test, PNA-LNA PCR Clamp, Cycleave, others | 89% concordance, 46% sensitivity and 97% specificity | (38) |
RGQ, rotor-gene Q; PNA-LNA, peptide nucleic acid-locked nucleic acid; EGFR, epidermal growth factor receptor; cfDNA, cell-free DNA; PCR, polymerase-chain-reaction; NSCLC, non-small cell lung cancer; TKI, tyrosine kinase inhibitor; EURTAC, the European Tarceva versus Chemotherapy; PFS, progression-free survival;