Table 1.
Major prospective clinical trials with positive results for the treatment of unresectable intrahepatic cholangiocarcinoma and biliary tract cancer.
| Regimen | Mechanism | Trial | Phase | Author | Report Year | Patient Number | ORR (%) | Median PFS (Month) | Median OS (Month) | Treatment Line | Conditions | References |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| GemCis | Cytotoxic anticancer | ABC-02 | III | Valle J | 2010 | 204 | 26 | 8 | 11.7 | 1st | [10] | |
| GemCis | Cytotoxic anticancer | BT22 | II | Furuse T | 2011 | 41 | 20 | 5.8 | 11.2 | 1st | [11] | |
| Pertuzumab + trastuzumab | Anti-ERBB(HER)2 | MyPathway | II | Hainsworth JD | 2018 | 7 | 29 | ND | ND | 2nd | Gene alteration | [31] |
| Larotrectinib | Anti-NTRK A/B/C | - | I/II | Drilon A | 2018 | 2 | 50 | ND | ND | 2nd | Gene alteration | [32] |
| GemCis | Cytotoxic anticancer | JCOG1113 | III | Morizane C | 2019 | 175 | 32.4 | 5.8 | 13.4 | 1st/2nd | [33] | |
| Gem + S-1 | Cytotoxic anticancer | JCOG1113 | III | Morizane C | 2019 | 179 | 29.8 | 6.8 | 15.1 | 1st/2nd | [33] | |
| Pemigatinib | Anti-FGFR1/2/3 | FIGHT-202 | II | Abou-Alfa GK | 2020 | 107 | 35.5 | 6.9 | 21.1 | 2nd | Gene alteration | [34] |
| Ivosidenib | Anti-IDH1 | ClarIDHy | III | Abou-Alfa GK | 2020 | 124 | 2.4 | 2.7 | 10.8 | 2nd | Gene alteration | [35] |
| Dabrafenib + trametinib | Anti-B-Raf + anti-MEK | ROAR | II | Subbiah V | 2020 | 43 | 47 | 9 | 14 | 2nd | Gene alteration | [36] |
| Entrectinib | Anti-NTRK A/B/C | STARTRK-1&2 | I/II | Doebele RC | 2020 | 1 | 100 | ND | ND | 2nd | Gene alteration | [37] |
| Bintrafusp alfa | Anti-PD-L1 + anti-TGFBR2 | NEOBIL | I | Yoo C | 2020 | 30 | 20 | 2.5 | 12.7 | 2nd | [38] | |
| Pembrolizumab | Anti-PD-1 | KEYNOTE-028 | Ib | Piha-Paul SA | 2020 | 24 | 13 | 1.8 | 5.7 | 2nd | MSI-high, PD-L1-positive | [39] |
| Pembrolizumab | Anti-PD-1 | KEYNOTE-158 | II | Piha-Paul SA | 2020 | 104 | 5.8 | 2 | 7.4 | 2nd | MSI-high | [39] |
| Folinic acid + fluorouracil + oxaliplatin | Cytotoxic anticancer | ABC-06 | III | Lamarca A | 2021 | 81 | 5 | ND | 6.2 | 2nd | [40] | |
| Infigratinib | Anti-FGFR1/2/3 | - | II | Javle M | 2021 | 122 | 23.1 | 6.7 | ND | 2nd | Gene alteration | [41] |
| Nivolumab | Anti-PD-1 | OPAL | II | ND | 2022 | 16 | ND | ND | ND | 2nd | * Interim analysis | ND |
| GemCis + S-1 | Cytotoxic anticancer | KHBO1401 | III | Ioka T | 2022 | 123 | 41.5 | 7.4 | 13.5 | 1st | [42] | |
| Durvalumab + GemCis | Cytotoxic anticancer + anti-PD-L1 | - | II | Oh DY | 2022 | 49 | 72 | 11 | 18.1 | 1st | [43] | |
| Durvalumab + GemCis | Cytotoxic anticancer + anti-PD-L1 | TOPAZ-1 | III | Oh DY | 2022 | 341 | 26.7 | 7.2 | 12.8 | 1st | Interim analysis | [12] |
| Futibatinib | Anti-FGFR1/2/3 | TAS-120 | II | Goyal L | 2023 | 103 | 42 | 9 | 21.7 | 2nd | Gene alteration | [44] |
| Pembrolizumab + GemCis | Anti-PD-1 + cytotoxic anticancer | KEYNOTE-966 | III | Kelley RK | 2023 | 533 | ND | 6.5 | 12.7 | 1st | [45] | |
| Atezolizumab + bevacizumab + GemCis | Cytotoxic anticancer + anti-PD-L1 + anti-VEGF | IMbrave151 | II | Shemesh CS | 2023 | 78 | ND | ND | ND | 1st | Interim analysis | [46] |
Blue, precision medicine; red, immune-checkpoint inhibitor; Cis, cisplatin; CTLA, cytotoxic T lymphocyte-associated protein; ERBB, erythroblastic oncogene B; FGFR, fibroblast growth factor receptor; Gem, gemcitabine; HER, human epidermal growth factor receptor; IDH, isocitrate dehydrogenase; MEK, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase; MSI, microsatellite instability; ND, no data; NTRK, neurotrophic tyrosine receptor kinase; ORR, objective response rate; OS, overall survival; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; PFS, progression-free survival; Raf, serine/threonine-protein kinase; S-1, oral 5-fluorouracil; TGFBR, transforming growth factor beta receptor; * occurred at a printing company (chlorinated solvent) in Osaka, Japan (UMIN000034931).