Table 3 The key reported clinical trials of of PD-1/PD-L inhibitors in patients with hepatocellular carcinoma and biliary tract cancer

HCC

PD-L1

Durvalumab

Phase I/II

NCT01693562

39

ORR 10.3%; DCR 33.3%; median OS 13.2 months; 9-month OS rate 62.3%; 12-month OS rate 56.4%

All grades 80.0%, including fatigue, pruritus, elevated AST; Grades 3–4 20.0%, including elevated AST and elevated ALT.

ASCO 2017 [131]

HCC

PD-1

Nivolumab

Phase I/II

NCT01658878

262

ORR 23% (sorafenib-naive), 16–19% (sorafenib-experienced); DCR 63% (sorafenib-naive); 12- month OS rate 73% (sorafenib-naive), 60% (sorafenib-experienced)

All grade 77%; Grade ≥3 23.5%, including elevated AST and elevated ALT.

ASCO 2017 [157]

HCC

PD-1

Nivolumab

Phase I/II

NCT01658878

262

ORR 20% (dose expansion phase), 23% (sorafenib-naive), 21% sorafenib-treated); median DOR: 9.9 months (dose expansion phase), DCR 64% (dose expansion phase); 9-month OS rate 74% (dose expansion phase)

Grades 3–4 20%

ASCO 2017 [158]

HCC

PD-1

Nivolumab

Phase I/II

NCT01658878

48

ORR 15%; median OS 15.1 months; median DOR 23.7 months; 12-month OS rate 59%; 18-month OS rate 48%

All grade 77%, including rash and AST increase; Grades 3–4 20%, including AST increase, lipase and ALT increase

ASCO 2016 [159]

HCC

PD-1

Nivolumab

Phase I/II

NCT01658878

39

ORR 23%; CR 5%; PR 18%; 6-month OS rate 72%

Any grade 71%, including AST increase, amylase increase, rash, ALT and lipase increase; grades 3–4 17%, including AST increase, ALT increase and lipase increase

ASCO 2015 [160]

HCC

PD-L1

Durvalumab

Phase I/II

NCT01693562

21

12-month DCR 21%

Any grade (multiple cancer types) 33%, including fatigue, nausea, rash, vomiting, and pyrexia; grade ≥3 (multiple cancer types) 7%

ASCO 2014 [61]

BTC

PD-1

Pembrolizumab

Phase Ib

NCT02054806

24

ORR 17%; SD 17%; PD 17%

All grade 63%, including pyrexia and nausea; grades 3–4 17%, including anemia, autoimmune hemolytic anemia, colitis, and dermatitis

ECCO 2015 [55]