Table 2. Clinical validity of F1CDx via non-inferiority for companion diagnostic claims.
| Disease Indication | Biomarker | Therapy | PPA, % (95% CI) | NPA, % (95% CI) | Comparator Assay | Detailed Concordance Results |
|---|---|---|---|---|---|---|
| NSCLC | EGFR exon 19 deletions and exon 21 L858R | afatinib, gefitinib, osimertinib, erlotinib | 98.1 (93.5, 99.8) | 99.4 (96.4, 100.0) | cobas® EGFR Mutation Test v2 (Roche Molecular Systems) | Tables S4-S6 in S1 Appendix |
| NSCLC | EGFR T790M | osimertinib | 98.9 (93.8, 100.0) | 86.1 (78.1, 92.0) | cobas® EGFR mutation Test v2 (Roche Molecular Systems) | Tables S7-S9 in S1 Appendix |
| NSCLC | ALK rearrangementsa | alectinib, crizotinib, ceritinib, brigatinib | 92.9 (85.1, 97.3) | 100 (95.2, 100.0) | Ventana ALK (D5F3) CDx Assay | Tables S10-S12 in S1 Appendix |
| Vysis ALK Break Apart FISH Probe Kit | ||||||
| Breast cancer | ERBB2 (HER2) amplification | trastuzumab, ado-trastuzumab emtansine, pertuzumab | 89.4 (82.2, 94.4) | 98.4 (95.3, 99.7) | HER2 FISH PharmDx® Kit (Dako Denmark, A/S) | Tables S13-S15 in S1 Appendix |
| CRC | KRAS wild-type | cetuximab, panitumumab | 100 (97.9, 100.0) | 100 (97.6, 100.0) | therascreen® KRAS RGQ PCR Kit (QIAGEN) | Tables S16-S18 in S1 Appendix |
| Melanoma | BRAF V600 mutation | dabrafenib, vemurafenib, trametinib, cobimetinib in combination with vemurafenib | 99.4 (166/167) | 89.6 (121/135)b | cobas® 4800 BRAF V600 mutation test (Roche Molecular Systems, Inc) | Tables S19-S21 in S1 Appendix |
| BRAF V600E mutation | 99.3 (149/150) | 99.2 (121/122) | ||||
| Melanoma | BRAF V600 dinucleotide | dabrafenib, vemurafenib, trametinib, cobimetinib in combination with vemurafenib | 96.3 (26/27) | 100 (24/24) | THxID® BRAF Kit (bioMérieux) | Table S22 in S1 Appendix |
CTA = clinical trial assay; FISH = fluorescence in situ hybridization; NPA = negative percent agreement; PPA = positive percent agreement; PCR = polymerase chain reaction.
a Samples evaluated were from a phase 3, multicenter, open-label study (NCT02075840) that evaluated the efficacy and safety of alectinib compared with crizotinib in treatment-naïve cancer patients with ALK rearrangements.
b The reported difference in NPA values for BRAF V600 and BRAF V600E is likely attributed to known sensitivity differences in the cobas BRAF mutation test, which has lower sensitivity for detection of dinucleotide V600 alterations than for the single nucleotide V600E c.1799T>A alteration, especially for samples in which F1CDx detected the nucleotides to be of lower than 40% mutational allele frequency, leading to low NPA values.