Table 2

Completed clinical trials with targeted therapies, alone or in combination with chemotherapy, in biliary tract cancers

Therapeutic regimen
(target)
AuthorsPatients (n)End points
EGFR
CetuximabRRPFSOS
GEM and cetuximab
First-line ph2
Borbath et al 34 4420.46 mPFS 4713.5
GEMOX and cetuximab
First-line, single-arm ph2
Gruenberger et al 35 3063%8.815.2
First-line versus GEMOX ph2Malka et al 36 15023 vs 296 vs 5.311 vs 12.4
First-line versus GEMOX ph2Chen et al 37 12227 vs 156.7 vs 4.110.6 vs 9.8
Second-line ph2Paule et al 38 933%EGFR low: 4 vs high: 7EGFR low: 7 vs high: 9
GEMCAP versus cetuximab
Anyline ph2
Rubovszky et al 39 3417.68.615.7
Panitumumab
GEMOX and panitumumab
First-line ph2 KRAS WT
Hezel et al 40 3145%10.620.3
GEMOX-CAP and panitumumab
Anyline ph2
Jensen et al 41 46338.310
GEM-IRINO and panitumumab
First-line ph2
Sohal et al 42 35399.712.9
GEMCIS and panitumumab versus GEMCIS in KRAS WT
First-line ph2
Vogel et al 43 9345 vs 39, pNS6.7 vs 8.2, pNS12.8 vs 21.4, pNS
Erlotinib
GEMOX and erlotinib versus GEMOX
First-line ph3
Lee et al 44 26830 vs 165.8 vs 4.29.5 vs 9.5
Docetaxel and erlotinib
Ph2
Chiorean et al 45 1105.7
Erlotinib
First-/Second-line ph2
Philip et al 46 4282.67.5
HER2
Lapatinib
First-/Second-line ph2
Ramanathan et al 47 1701.85.2
Trastuzumab
Second-line ph2
Kaseb48 450NRNR
GEMCIS and afatinib
First-line ph1b
Moehler et al 49 9NR158 days235 days
VEGF and multitarget
Bevacizumab
GEMOX and bevacizumab
First/Second ph2
Zhu et al 50 3540712.7
GEMCAP and bevacizumab
First-line ph2
Iyer et al 51 50728.111.3
Sorafenib
First-line ph2El-Khoueiry et al 52 31039
Anyline ph2Bengala et al 53 4622.34.4
GEM-sorafenib versus GEM
First-line ph2
Moehler et al 54 1028 vs 63 vs 4.98.4 vs 11.2
GEMCIS and sorafenib
First-line ph2
Lee et al 55 39NR6.514.4
Sunitinib
Second-line ph1Yi et al 56 5691.74.8
Second-line ph2Neuzillet et al 57 5315
DCR: 85
5.29.6
Cediranib
GEMCIS and cediranib versus GEMCIS
First-line ph2/3
Valle et al 58 12444 vs 198 vs 7.414.1 vs 11.9
Vandetanib
First-line ph2
Santoro et al 59 1734105 days228 days
FGFR
BGJ398 in CC with FGFR2
≥Second-line phase 2
Javle et al 60 2614
DCR: 82
NRNR
50% pts on study for >120 days
ODM-203Ahnert et al 61 24 (1 CC with FGFR fusion)8NRNR (>40 weeks for CC pt)
MAPK pathway
Selumetinib
First-/Second-line ph2
Bekaii-Saab et al 62 28123.79.8
GEMCIS and selumetinib
First-line ph1
Bridgewater et al 63 1237.56.4NR
TrametinibIoka et al 64 20510.6 weeksNR
1 pt>9m
Binemetinib and GEMCIS
First-line ph1
Lowery et al 65 12506.49.1
MK-2206
≥Second-line, ph2
Ahn et al 66 8NR1.73.5
c-MET
Tivantinib + gemcitabine
Anyline ph1
Pant et al 67 2020NRNR
Cabozanitib
≥Second-line ph2
Goyal et al 68 1901.85.2
Multiagent/Other
Bevacizumab and erlotinib
First-line ph2
Lubner et al 69 49124.49.9
Sorafenib and erlotinib
First-line ph2
El-Khoueiry et al 70 34726
Bortezomib
Second-/Third-line ph2
Denlinger et al 71 2051.69.5
Pazopanib and trametinib
≥Second-line ph1b
Shroff et al 72 255
DCR: 75
4.36.7
GEMOX-CAP and panitumumab versus bev
First-line with crossover at PD
Jensen et al 73 8846 vs 186.1 vs 8.29.5 vs 12.3
IDH1
AG-120Burris et al 74 205
DCR: 60
NR5 SD>6 months
WNT pathway
DKN-01
First-line ph1
Eads et al 75 22 ongoing
abstract
33% (3 from 9 evaluable)NRNR
Solid tumour studies
GDC-0919 (IDO1)Nayak et al 76 19 (1 CC)NRNR1 CC SD>225 days
  • CAP, capecitabine; CIS, cisplatin; DCR, disease control rate; EGFR, epidermal growth factor receptor; FGFR, fibroblast growth factor receptor; GEM, gemcitabine; HER2, human epidermal growth factor receptor 2; IDH, isocitrate dehydrogenase; IRINO, irinotecan; KRAS, Kirsten rat sarcoma viral oncogene homologue; MAPK, mitogen-activated protein kinase; OS, overall survival; OX, oxaliplatin; PD, progressive disease; PFS, progression-free survival; ph, phase; RR, response rate; VEGF, vascular endothelial growth factor; WT, wild-type.