Table 2.
Chemotherapy Regimens and Outcomes.
| Author, Year, Study | Patients, Country |
Location of BTC | Treatment Arm | () |
|---|---|---|---|---|
| ADJUVANT THERAPY | ||||
| Siebenhüner, 2018 Phase 2 [56] |
30 Switzerland |
Intrahepatic (57%) Extrahepatic (20%) Other (24%) |
GC vs. gem | Median OS: no difference |
| Primrose, 2019 Phase 3 [57] |
447 UK |
Intrahepatic (19%) Extrahepatic (64%) Other (17%) |
Capecitabine vs. surveillance | Median OS: 51.1 vs. 36.4 HR for OS: 0.71 (0.55–0.92) (p = 0.010) Median RFS: 24.4 vs. 17.5 |
| Edeline, 2019 Phase 3 [58] |
196 France |
Intrahepatic (44%) Extrahepatic (36%) Other (20%) |
GEMOX vs. surveillance | Median OS: no difference Median RFS: no difference |
| THERAPEUTIC | ||||
| Valle, 2010 Phase 3 [59] |
410 UK |
CCA * (59%) Other (41%) |
GC vs. gem | Median OS: 11.7 vs. 8.1 HR for OS: 0.64 (0.52–0.80) (p < 0.001) Median PFS 8.0 vs. 5.0 (p < 0.001) |
| Okusaka, 2010 Phase 2 [60] |
83 Japan |
Intrahepatic (34%) Extrahepatic (23%) Other (43%) |
GC vs. gem | Median OS: 11.2 vs. 7.7 Median PFS: 6.8 vs. 3.7 HR for PFS: 0.66 (0.41–1.05) (p = 0.077) |
| Kim, 2019 Phase 3 [61] |
222 South Korea |
CCA * (73%) Other (27%) |
XELOX vs. GEMOX | Median OS: no difference ORR: no difference |
| Lamarca, 2019 Phase 3 [62] |
162 UK |
Intrahepatic (44%) Extrahepatic (28%) Other (28%) |
Oxaliplatin + 5-FU + symptom control vs. symptom control | Median OS: 6.2 vs. 5.3 HR for OS: 0.69 (0.50–0.97) (p = 0.031) |
| TARGETED THERAPY | ||||
| Valle, 2015 Phase 2 [63] |
124 UK |
Intrahepatic (23%) Extrahepatic (39%) Other (38%) |
Cediranib (anti-VEGF) + GC vs. GC | Median PFS: no difference |
| Abou-Alfa, 2020 Phase 2 [64] |
146 Global |
Intrahepatic (89%) Extrahepatic (8%) Other (3%) |
Pemigatinib (anti-FGFR) + with or without FGF fusion/rearrangement |
Median OS: 21.1 vs. 4.0 OR: 35.5% vs. 0% Median PFS: 6.9 vs. 1.7 |
| Rizzo, 2020 Retrospective study [65] |
450 Global |
Intrahepatic (64%) Extrahepatic (18%) Other (18%) |
EGFR inhibitor + gem vs. gem | Median OS: no difference Median PFS: no difference ORR: no difference |
| Ueno, 2020 Phase 2 [66] |
26 Japan |
Intrahepatic (23%) Extrahepatic (31%) Other (46%) |
Lenvatinib (anti-VEGF) | Median OS: 7.36 ORR: 11.5% (3.2–27.2) Median PFS: 3.19 |
| Abou-Alfa, 2020 Phase 3 [67] |
185 Global |
Intrahepatic (92%) Extrahepatic (3%) Other (5%) |
Ivosideninb (IDH1 inhibitor) vs. placebo | Median PFS: 2.7 vs. 1.4 (p < 0.001) HR for PFS: 0.37 (0.25–0.54) (p < 0.0001) Median OS: no difference |
| IMMUNOTHERAPY | ||||
| Piha-Paul, 2020 Phase 1b, 2 [68] |
104 (phase 2) 24 (phase 1b) Global |
Pembrolizumab (anti-PD1) | KEYNOTE-158 (phase 2) Median OS: 7.4 Median PFS: 2.0 KEYNOTE-028 (phase 1b) Median OS: 5.7 Median PFS: 1.8 |
|
| Kim, 2020 Phase 2 [69] |
54 USA |
Intrahepatic (59%) Extrahepatic (9%) Other (32%) |
Nivolumab (anti-PD1) | Median OS: 14.24 Median PFS: 3.68 ORR: 22% |
Abbreviations: Biliary tract cancer (BTC), cholangiocarcinoma (CCA), gemcitabine (Gem), gemcitabine + cisplatin (GC), gemcitabine + oxaliplatin (GEMOX), capecitabine + oxaliplatin (XELOX), gemcitabine + capecitabine (GemCap), gemcitabine+S1 (GS), overall survival (OS), progression-free survival (PFS), hazards ratio (HR), recurrence-free survival (RFS), objective response (OR), objective response rate (ORR), epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), vascular endothelial growth factor (VEGF). *, study did not differentiate between intrahepatic and extrahepatic cholangiocarcinoma.