TABLE 3.
Performance Characteristics of OncoBEAM RAS CRC Kit, Idylla ctKRAS, and Idylla ctNRAS-BRAF Mutation Tests
| OncoBEAM RAS CRC Kit | Idyllact KRAS Mutation Test | Idylla ctNRAS-BRAF Mutation Test | |
|---|---|---|---|
| CE Mark Approval Date | April 2016 | November 2017 | November 2017 |
| Technology | BEAMing digital PCR | Idylla real-time PCR | Idylla real-time PCR |
| Amount of Plasma Needed, mL | 3–4 | 1 | 1 |
| Hands-on Time, min | Dedicated technician | < 1 | < 1 |
| Turnaround Time | 1 wk | 130 min | 110 min |
| Gene Coverage | 34 mutations: 16 KRAS and 18 NRAS | 21 KRAS | 18 NRAS |
| Exon 2: codons 12 and 13 | Exon 2: codons 12 and 13 | Exon 2: codons 12 and 13 | |
| Exon 3: codons 59 and 61 | Exon 3: codons 59 and 61 | Exon 3: codons 59 and 61 | |
| Exon 4: codons 117 and 146 | Exon 4: codons 117 and 146 | Exon 4: codons 117 and 146 | |
| 5 BRAF | |||
| Exon 15: codon 600 | |||
| Sensitivity in Plasma, % | 0.02–0.04 | 0.5 | 0.5 |
| MAF Quantification | Quantitative | Semiquantitative | Semiquantitative |
| Clinical Validity Measures | OncoBEAM RAS CRC Kit, Instructions for | RASANC study (n = 198)45,46 | |
| Use OBMRASIVD37 | Comparator test: plasma-based NGS analysis with sensitivity of 0.2% | ||
| Tissue comparator test: standard of | KRAS+ (n = 84) | ||
| care tissue testing | NRAS+ (n = 6) | ||
| Sensitivity: 92.6% (112/121) | BRAF+ (n = 13) | ||
| Specificity: 94.0% (110/117) | RAS. Sensitivity: 97.8% (90/92) | ||
| Concordance: 93.3% (222/238) | RAS: Specificity: 95.3% (101/106) | ||
| Grasselli et al, 2017 (n = 146)38 | RAS: Concordance: 96.5% (191/198) | ||
| Tissue comparator test: PCR | KRAS: Concordance: 96% | ||
| Sensitivity: 89% | NRAS: Concordance: 100% | ||
| Specificity: 90% | BRAF: Concordance: 99.5% | ||
| Concordance: 89.7% | |||
| PPV: 84% | |||
| NPV: 93% | |||
| Vidal et al, 2017 (n = 115)39 | |||
| Tissue comparator test: comparison: | |||
| standard of care | |||
| Sensitivity: 92.6% (112/121) | |||
| Specificity: 94% (110/117) | |||
| Concordance: 93.3% (222/238) | |||
| Schmiegel et al, 2017 (n = 98)40 | |||
| Tissue comparator test: Sanger | |||
| sequencing | |||
| Sensitivity: 90.4% (47/52) | |||
| Specificity: 93.5% (43/46) | |||
| Concordance: 91.8% (90/98) | |||
| Normanno et al, 2017 (n = 92)43 | |||
| Tissue comparator test: NGS | |||
| Sensitivity: 69.7% | |||
| Specificity: 83.1% | |||
| Concordance: 78.3% (72/92) | |||
| PPV: 69.7%; 83.1% | |||
| Hahn et al, 2015 (n = 46)42 | |||
| Comparator tumor test: Sanger | |||
| sequencing or pyrosequencing | |||
| Sensitivity: 92% (23/25) | |||
| Specificity: 100% (21/21) | |||
| Concordance: 96% (44/46) | |||
| Clinical Outcome | Grasselli et al, 2017 (n = 146)38 | NR | |
| Median OS: | |||
| Tissue KRAS-wild-type: 39.1 mo | |||
| Tissue KRAS-mutated: 28.7 mo | |||
| Plasma KRAS-wild-type: 42.9 mo | |||
| Plasma KRAS mutated: 27.8 mo | |||
Abbreviations: CE, Conformité Européene; PCR, polymerase chain reaction; MAF, mutant allele frequency; PPV, positive predictive value; NPV, negative predictive value; NGS, next-generation sequencing; NR, not reported.