Table 2.
Fusions detected in ctDNA but not in tissue may represent acquired resistance mechanisms.
| Case | Disease | Days between specimen collection | Tissue biopsy | Liquid biopsy | Pre–liquid biopsy treatment and response |
|---|---|---|---|---|---|
| 1 | NSCLC | 75 | EGFR ex19del, C797S | EGFR ex19del | Gefitinib |
| EML4-ALK fusion | |||||
| 2 | NSCLC | 196 | EGFR L858R | EGFR L858R | NA |
| EML4-ALK fusion | |||||
| 3 | NSCLC | 775 | EGFR ex19del | EGFR ex19del | NA |
| EML4-ALK fusion | |||||
| 4 | NSCLC | 894 | EGFR L858R | EGFR L858R | Erlotinib (12 mo) – PR |
| PLEKHA7-ALK fusion | |||||
| Afatinib (2 mo) | |||||
| Osimertinib (12 mo) – PRa | |||||
| 5 | NSCLC | 454 | EGFR L858R, L833V | EGFR L858R, L833V, T790M | Erlotinib |
| FGFR2-CCDC6 fusion | |||||
| 6b | NSCLC | 133 | EGFR ex19del | EGFR ex19del | NA |
| FGFR3-TACC3 fusion | |||||
| 7 | NSCLC | 426 | EGFR L858R, E709K | EGFR L858R | Afatinib + cetuximab (10 mo) – SDa |
| FGFR3-TACC3 fusion | |||||
| 8 | NSCLC | 464 | EGFR ex19del, T790M | EGFR ex19del, T790M, C797G | Osimertinib (7 mo) - SD |
| BRAF V600E | |||||
| FGFR3-ADD1 fusion | |||||
| 9b | NSCLC | 13 | EGFR ex19del | EGFR ex19del | NA |
| ERC1-RET fusion | |||||
| 10 | NSCLC | 686 | EGFR ex19del, T790M | EGFR ex19del | Osimertinib (8 mo) |
| NCOA4-RET fusion | |||||
| 11 | CRC | 850 | KRAS WT | EGFR amp | FOLFOX, capecitabine, Lonsurf, ramucirumab, bevacizumab, Panitumumab |
| MAP2K1 I103_K104del | |||||
| NF1 truncation | |||||
| EML4-ALK fusion | |||||
| 12b | CRC | 31 | KRAS WT | EGFR V441G, G465E/R | NA |
| MET amp | NRAS G13D, Q61K | ||||
| KRAS G12C | |||||
| ZC3HAV1-BRAF fusion | |||||
| 13 | CRC | 615 | KRAS WT | EGFR S492R | NA |
| KRAS G12V, Q61H | |||||
| NRAS Q61K/L | |||||
| MAP2K1 Q58del, I111T | |||||
| MAP2K2 F57V | |||||
| NF1 F945fs*9 | |||||
| MKRN1-BRAF fusion | |||||
| 14 | CRC | 1,014 | KRAS G13D | KRAS G13D | FOLFOX, 5FU maintenance, FOLFIRI, regorafenib |
| DENND2A-BRAF fusion | |||||
| 15 | CRC | 2,959 | KRAS WT | NRAS Q61K | NA |
| TRIM24-BRAF fusion | |||||
| 16 | CRC | 150 | KRAS WT | KRAS G12A, Q61H | NA |
| NRAS G12D | |||||
| MAP2K1 E102_I103del | |||||
| PDE7A-EGFR fusion | |||||
| 17 | CRC | 854 | KRAS WT | BRAF V600E | FOLFIRI + bevacizumab (4 mo) |
| EGFR V441G, S492R | |||||
| HRAS Q61L | FOLFIRI + cetuximab (6 mo) | ||||
| MAP2K1 K57T, E102_I103del | FOLFOX + bevacizumab (11 mo) | ||||
| NRAS Q61K | |||||
| FGFR3-TACC3 fusion | Pembrolizumab + regorafenib | ||||
| GOLGA3-BRAF fusion | |||||
| SYN2-RAF1 fusion | |||||
| 18c | CRC | 1,912 | KRAS G12C | KRAS G12C, G13D | Adagrasib |
| MAP2K1 E102_I103del | Adagrasib + cetuximab | ||||
| NRAS Q61K | |||||
| AKAP9-BRAF fusion | |||||
| FGFR3-TACC3 fusion | |||||
| RAF1-TRAK1 fusion | |||||
| RAF1-CCDC176 fusion | |||||
| 19 | CRC | 1,236 | KRAS WT | KRAS Q61H | NA |
| EGFR amp | |||||
| MET-CAPZA2 fusion | |||||
| 20 | Breast | 1,269 | ER+/PR+ | ESR1 Y537N, D538G | Everolimus, denosumab, fulvestrant |
| AKT1 E17K | |||||
| FGFR3-TACC3 fusion | |||||
| 21 | Breast | 1,591 | PIK3CA E542K | PIK3CA E542K | NA |
| ESR1 E380Q | |||||
| KRAS G12C | |||||
| PTEN S59*, M134I | |||||
| BAIAP2L1-RET fusion |
aSchrock AB, Zhu VW, Hsieh WS, et al. Receptor tyrosine kinase fusions and BRAF kinase fusions are rare but actionable resistance mechanisms to EGFR tyrosine kinase inhibitors. J Thorac Oncol 2018;13:1312–23.
bThese patients had their liquid specimen collected before the tissue specimen and the fusions may represent subclonal resistance not captured in the subsequent tissue biopsy. All other patient pairs had the fusion-negative tissue collected first.
cAwad MA, Liu S, Rybkin II, et al. Acquired resistance to KRASG12C inhibition in cancer. 2021 Jun 24;384(25):2382–2393.