Table 1.
Results of selected studies testing immune checkpoint inhibitors in advanced HCC patients.
| Study (Year) | Phase | n | Population | Drug | Median overall Survival | Median Progression-Free Survival | Objective Response Rate |
|---|---|---|---|---|---|---|---|
| CheckMate 459 (2019) [23] | III | 743 | Unresectable Child–Pugh A HCC naïve to systemic treatment | Nivolumab vs. sorafenib | 16.4 mo for nivolumab vs. 14.7 mo for sorafenib (HR: 0.85; p = 0.0752) | 3.7 mo for nivolumab vs. 3.8 mo for sorafenib | 15% for nivolumab and 7% to sorafenib |
| CheckMate 040 (2017) [24] | I/II | 262 (dose escalation: 48 and dose expansion: 216) | Advanced HCC with or without HBV or HCV, Child–Pugh A or B7 after sorafenib failure or intolerance | Nivolumab | Dose escalation phase: 15.0 mo Dose expansion phase: 9-mo OS rate: 74% |
Dose escalation phase: 3.4 mo Dose expansion phase: 4.1 mo |
Dose escalation phase: 15% Dose expansion phase: 20% |
| KEYNOTE-224 (2018) [26] | II | 104 | Advanced HCC, Child–Pugh A after sorafenib failure or intolerance | Pembrolizumab | 12.9 mo | 4.9 mo | 17% |
| KEYNOTE-240 (2020) [27] | III | 413 | Advanced HCC, Child–Pugh A after sorafenib failure or intolerance | Pembrolizumab vs. placebo | 13.9 mo for pembrolizumab vs. 10.3 mo for placebo group (HR: 0.78; p = 0.0238) | 3.0 mo in the pembrolizumab group vs. 2.8 mo in the placebo group (HR: 0.775; p = 0.0186) | 16.9% for pembrolizumab vs. 2.2% for placebo |
| Wainberg et al. (2017) [28] | I/II | 40 | Advanced HCC, Child–Pugh A after sorafenib failure or intolerance | Durvalumab | 13.2 mo | 10% | |
| Kelley et al. (2020) [29] | II | 104 | Advanced HCC after sorafenib failure or intolerance | Durvalumab | 11.7 mo | 9.6% | |
| Sangro et al. (2013) [30] | II | 20 | HCV-related advanced HCC, Child–Pugh A or B | Tremelimumab | 8.2 mo | 6.48 mo | 17,6% |
| Kelley et al. (2020) [29] | II | 159 | Advanced HCC after sorafenib failure or intolerance to sorafenib | Tremelimumab | 17.1 mo | 7.2% | |
| Qin et al. (2020) [32] | II | 217 | Advanced HCC, Child–Pugh A or B7 after sorafenib failure or intolerance to first-line systemic therapy | Camrelizumab | 13.8 mo | 2.1 mo | 14.7% |
| He et al. (2018) [33] | Ib | 26 | Advanced HCC, Child–Pugh A after failure or intolerance to first-line systemic therapy | Cemiplimab | 3.7 mo | 19.2% | |
| Checkmate 040 (2020) [35] | II | 148 | Advanced HCC patients, Child–Pugh A previously treated or intolerant to sorafenib | Nivolumab + ipilimumab | Arm A: 22.8 mo Arm B: 12.5 mo Arm C: 12.7 mo |
Arm A: 32% Arm B: 27% Arm C: 29% |
|
| Kelley et al. (2017) [36] | I/II | 40 | Advanced HCC with or without HBV or HCV, Child–Pugh A or B; 70% were previously treated. | Durvalumab + tremelimumab | 15% for all patients and 30% for uninfected patients | ||
| Kelley et al. (2020) [29] | II | 159 | Advanced HCC who progressed on, were intolerant to, or refused sorafenib | Durvalumab + tremelimumab | 18.7 mo for tremelimumab 300 mg + durvalumab and 11.3 months for tremelimumab 75 mg + durvalumab | 22.7% for tremelimumab 300 mg + durvalumab and 9.5% for tremelimumab 75 mg + durvalumab |
Abbreviations: HCC: hepatocellular carcinoma; mo: months; HR: hazard ratio; HBV: hepatitis B virus; HCV: hepatitis C virus; vs.: versus; NR: not reached; BCLC: Barcelona Clinic Liver Cancer; OS: overall survival.