Table 3.
Efficacy of the most common targeted agents evaluated in pretreated advanced CCA
| Gene | Type of alteration | Frequency (%) | Drug | Phase of trial | ORR (%) | DCR (%) | Median PFS (months) | Median OS (months) |
|---|---|---|---|---|---|---|---|---|
| IDH1 | Mutation | 15-20 | Ivosidenib58 | III | 2.0 | 53.0 | 2.7 | 10.3 |
| FGFR2 | Rearrangement | 10 | Pemigatinib67,68 | II | 37.0 | 82.4 | 7.0 | |
| Futibatinib71 | II | 42.0 | 83.0 | 9.0 | 17.5 | |||
| Infigratinib75,76 | II | 23.1 | 84.3 | 7.3 | 21.7 | |||
| Derazantinib79 | II | 20.7 | 82.8 | 5.7 | 12.2 | |||
| HER2 | Amplification | 5-10 | Trastuzumab + pertuzumab87 | II | 23.0 | 51.0 | 4.0 | NR |
| Zanidatamab89 | IIb | 41.3 | 68.8 | 5.5 | ||||
| Trastuzumab deruxtecan91 | II | 22.0 | 65.9 | 4.6 | ||||
| BRAF | Mutation | 3 | Dabrafenib + trametinib95 | II | 53.0 | NA | 9.0 | 13.5 |
| NTRK | Rearrangement | 1 | Entrectinib97 | I/II | 57.0 | NA | 11.2 | 21.0 |
| Larotrectinib98 | I/II | 79.0 | NA | 28.3 | 44.4 | |||
| RET | Rearrangement | 1 | Pralsetinib99 | I/II | 57.0 | 83.0 | 7.4 | 23.5 |
| Selpercatinib100 | I/II | 43.9 | NA | 13.2 | NA | |||
| KRAS | Mutation | 1 | Adagrasib101 | II | 41.7 | 91.7 | 8.6 | 15.1 |
CCA, cholangiocarcinoma; ORR, objective response rate; DCR, disease control rate; PFS, progression-free survival; OS, overall survival; IDH1, isocitrate dehydrogenase 1; FGFR2, fibroblast growth factor receptor 2; NR, not reached; HER2, human epidermal growth factor receptor 2; BRAF, proto-oncogene BRaf; NA, not available; NTRK, neurotrophic tropomyosin receptor kinase; RET, rearranged during transfection; KRAS, Kirsten rat sarcoma virus.