Table 1.
Baseline characteristics of included studies with anti-PD1/PDL1 in aBTC.
| Study | Region | Study type | Median follow-up, months | Disease status | Drug | Clinical setting | Line of therapy | Sample size | Median age (range), years | Male, % |
|---|---|---|---|---|---|---|---|---|---|---|
| Kim et al. (32)/NCT02829918 | USA | Open-label, multi-institutional, single-group, phase 2 | 12.4 | Advanced refractory BTC | Nivolumab | 240 mg, i.v., Q2W for 16 weeks, and then 480 mg, i.v., Q4W | 2nd line and beyond | 54 | 65 (28–86) | 50 |
| Ueno et al. (39)/JapicCTI-153098 | Japan | Open-label, multicenter, non-randomized, phase 1 | 5.1 | Unresectable or recurrent BTC | 1) Nivolumab | 240 mg, i.v., Q2W | 2nd line and beyond | 30 | 68.0 | 60 |
| 8.2 | Unresectable or recurrent BTC | 2) Nivolumab + GemCis | Nivolumab 240 mg, i.v., Q2W + cisplatin 25 mg/m2, i.v. + gemcitabine 1,000 mg/m2, i.v. | 1st-line | 30 | 67.5 | 47 | |||
| Lee et al. (42) | Korea | Multicenter retrospective study | 3.8 | PDL1-positive GemCis-refractory BTC | Pembrolizumab | 200 mg, i.v., Q3W | 2nd line and beyond | 51 | 66 (43–83) | 56.9 |
| Kang et al. (33)/NCT03695952 | Korea | Single-center, prospective cohort study | 9.6 | PDL1-positive advanced refractory BTC | Pembrolizumab | 200 mg, i.v., Q3W | 2nd line and beyond | 40 | 61 (41–76) | 57.5 |
| KEYNOTE-028/NCT02054806 (40, 41) | NR | Open-label, multicenter, non-randomized, phase 1b | 5.7 | aBTC | Pembrolizumab | 10 mg/kg, Q2W for ≤2 years | 2nd line and beyond | 24 | 64 (43–70) | 58.3 |
| KEYNOTE-158/NCT02628067 (40) | NR | Open-label, multicenter, non-randomized, phase 2 | 7.5 | aBTC | Pembrolizumab | 200 mg, Q3W | 2nd line and beyond | 104 | 63 (34–81) | 49.0 |
| Sun et al. (43) | China | Single-center, retrospective study | NR | aBTC | 1) PD1 inhibitor monotherapy | NR | 2nd line and beyond | 20 | NR | 55 |
| NR | aBTC | 2) PD1 inhibitor + chemotherapy | NR | 2nd line and beyond | 38 | NR | 63.2 | |||
| Yarchoan et al. (46)/NCT03201458 | USA | Randomized, open-label, multicenter, phase 2 | NR | aBTC | atezolizumab | 840 mg, i.v., Q2W | 2nd line and beyond | 39 | NR | NR |
| Ioka et al. (48)/NCT01938612 | Asia | Open-label, multicenter, phase 1 | NR | aBTC | 1) Durvalumab | 10 mg/kg, Q2W | 2nd line and beyond | 42 | 64 | NR |
| NR | aBTC | 2) Durvalumab + tremelimumab | durvalumab 20 mg/kg + tremelimumab 1.0 mg/kg, Q4W | 2nd line and beyond | 65 | 62 | NR | |||
| Yoo et al. (31)/NCT02699515 | Japan, Korea, Taiwan | Open-label, phase 1 | 15.3 | Metastatic or locally advanced BTC | Bintrafusp alpha | 1,200 mg, i.v., Q2W | 2nd line and beyond | 30 | 67 | 63 |
| Merck et al. (49)/NCT03833661 | NR | Open-label, multicenter, single-group, phase 2 | NR | Locally advanced or metastatic BTC | Bintrafusp alpha | 1,200 mg, i.v., Q2W | 2nd line | 159 | NR | NR |
| Villanueva et al. (51)/NCT03797326 | NR | Open-label, non-randomized, phase 2 | NR | aBTC | Pembrolizumab + lenvatinib | Pembrolizumab 200 mg, Q3W + lenvatinib 20 mg, q.d. | 2nd line and beyond | 31 | NR | NR |
| Lin et al. (35)/NCT03895970 | NR | Single-arm | 9.5 | aBTC | Pembrolizumab + lenvatinib | Pembrolizumab 200 mg, Q3W (n = 11) or 3 mg/kg, Q3W (n = 21) + lenvatinib 12 mg (body weight ≥ 60 kg) or 8 mg (body weight < 60 kg), p.o., q.d. | 2nd line and beyond | 32 | 56.5 | 56 |
| Arkenau et al. (36)/NCT02443324 | 5 countries | Open-label, multicenter, non-randomized, phase 1 | 15.7 | Previously treated advanced or metastatic BTC | Pembrolizumab + ramucirumab | Pembrolizumab 200 mg, i.v., d1, Q3W + ramucirumab 8 mg/kg, i.v., d1, d8 | 2nd line and beyond | 26 | 63 (36–78) | 30.8 |
| Wang et al. (34)/NCT04642664 | China | Open-label, single-center, non-randomized, prospective | 13.4 | Previously treated aBTC | Camrelizumab + apatinib | Camrelizumab 200 mg, i.v., Q3W + apatinib 250 mg, p.o., q.d. | 2nd line and beyond | 22 | 60 (39–72) | 52.4 |
| Zong et al. (52)/ChiCTR1900022003 | China | Phase 2 | 8.76 | Previously treated aBTC | Sintilimab + anlotinib | Sintilimab 200 mg, i.v., d1, Q3W + anlotinib 12 mg, p.o., d1~d14, Q3W | 2nd line | 17 | 59 (43–69) | 52.9 |
| Zhou et al. (50)/NCT03996408 | China | Open-label, dose-escalating, dose-expansion, phase 1b | NR | Advanced refractory BTC | TQB2450 + anlotinib | Anlotinib 10 mg and then 12 mg, p.o., d1~d14, Q3W + TQB2450 1,200 mg, i.v., d1, Q3W | 2nd line and beyond | 25 | NR | NR |
| Sun et al. (53)/NCT03825705 | China | phase 1b | 14.9 | aBTC | TQB2450 + anlotinib | Anlotinib 10 mg (n = 22) or 12 mg (n = 12), d1~d14, Q3W + TQB2450 1,200 mg, Q3W | 2nd line | 34 | 57 (37–72) | 44.1 |
| Cousin et al. (54)/NCT03475953 | France | Open-label, multicenter, single-arm, phase 2 | 9.8 | Advanced refractory BTC | Avelumab + regorafenib | Regorafenib 160 mg, q.d., d1~d21, Q4W + avelumab 10 mg/kg, Q2W | 2nd line and beyond | 34 | 63 (36–80) | NR |
| Oh et al. (47)/NCT03046862 | Korea | Phase 2 | 28.5 | Chemo-naive aBTC | 1) Durvalumab + tremelimumab + GemCis (biomarker cohort) | Gemcitabine 1,000 mg/m2 + cisplatin 25 mg/m2, d1, d8, followed by GemCis + durvalumab 1,120 mg + tremelimumab 75 mg, Q3W | 1st line | 30 | NR | NR |
| 11.9 | Chemo-naive aBTC | 2) Durvalumab + tremelimumab + GemCis | NR | 1st line | 46 | NR | NR | |||
| 11.3 | Chemo-naive aBTC | 3) Durvalumab + GemCis | NR | 1st line | 45 | NR | NR | |||
| Boileve et al. (60)/NCT03704480 | France | Safety run-in results of the randomized IMMUNOBIL PRODIGE 57 phase 2 trial | NR | aBTC | 1) Durvalumab + tremelimumab | Durvalumab 1,500 mg, i.v., d1 + tremelimumab 75 mg, i.v., d1, Q4W | 2nd line | 10 | 67 (60–75) | 50 |
| 9.8 | aBTC | 2) Durvalumab + tremelimumab + paclitaxel | Durvalumab 1,500 mg, i.v., d1 + tremelimumab 75 mg, i.v., d1, Q4W + paclitaxel 80 mg/m2, i.v., d1, d8, d15 | 2nd line | 10 | 70 (61–75) | 70 | |||
| Floudas et al. (55)/NCT02821754 | USA | Non-randomized, phase 2 | NR | aBTC | Durvalumab + tremelimumab | Tremelimumab 75 mg, Q4W + durvalumab 1,500 mg for 4 doses, followed by durvalumab monotherapy 1,500 mg, Q4W | NR | 12 | NR | NR |
| Klein et al. (37)/NCT02923934 | Australia | Open-label, multicenter, non-randomized, phase 2 | NR | aBTC | Nivolumab + ipilimumab | Nivolumab 3 mg/kg + ipilimumab 1 mg/kg, Q3W for 4 doses, followed by nivolumab monotherapy 3 mg/kg, Q2W | 2nd line and beyond | 39 | 65 (37–81) | 51 |
| Chiang et al. (58)/NCT04172402 | Taiwan | Single arm, phase 2 | 6.4 | aBTC | Nivolumab + GS | Nivolumab 240 mg + gemcitabine 800 mg/m2, d1 + S-1 80/100/120 mg, q.d., d1~d10, Q2W | 1st line | 48 | 66 (30–80) | 46 |
| Liu et al. (56)/NCT03796429 | China | Open-label, phase 2 | 10 | aBTC | Toripalimab + GS | Toripalimab 240 mg, i.v., Q3W + gemcitabine 1,000 mg/m2, i.v., d1, d8 + S-1 40–60 mg, b.i.d. * 14 days, Q3W | 1st line | 39 | 64 | 48.7 |
| Chen et al. (38)/NCT03486678 | China | Open-label, single-arm, phase 2 | 11.8 | aBTC | Camrelizumab + GEMOX | Camrelizumab 3 mg/kg, total dose ≤200 mg, i.v. drip, d1 + gemcitabine 800 mg/m2, i.v. drip, d1 + oxaliplatin 85 mg/m2, i.v. drip, d2, Q2W | 1st line | 37 | 64 (41–74) | 70.3 |
| Qin et al. (57)/NCT0309289 | China | Multicenter, single-arm, phase 2 | NR | aBTC | Camrelizumab + FOLFOX4 or GEMOX | Camrelizumab 3 mg/kg, i.v., Q2W + typical FOLFOX4 or GEMOX | 1st line | 43 | NR | NR |
| Gou et al. (59) | China | Retrospective study | NR | aBTC | PD1 inhibitors + nab-paclitaxel + S-1 | NR | 1st line | 32 | NR | NR |
PD1, programmed cell death protein 1; PDL1, programmed cell death ligand 1; aBTC, advanced biliary tract cancer; BTC, biliary tract cancer; USA, United States; GemCis, gemcitabine + cisplatin; S-1, tegafur-gimeracil-oteracil; GS, gemcitabine + tegafur-gimeracil-oteracil; GEMOX, gemcitabine + oxaliplatin; FOLFOX4, fluorouracil + leucovorin + oxaliplatin; i.v., intravenously; i.v. drip, intravenous drips; p.o., orally; q.d., once daily; b.i.d., twice daily; Q2W, every 2 weeks; Q3W, every 3 weeks; Q4W, every 4 weeks; d1, day 1; d2, day 2; d8, day 8; d10, day 10; d14, day 14; d15, day 15; d21, day 21; 1st, first; 2nd, second; NR, not reported.