Table 4.
Systemic therapies for HCC: summary of subgroup analyses of HBV versus HCV versus non-viral HCC in key phase III studies
| Trial | Treatment | Trial aetiology (n, %) | Overall survival HR (95% CI) | Progression-free survival HR (95% CI) |
|---|---|---|---|---|
| Immunotherapies — first line | ||||
| IMbrave150 (ref. 190) | Atezolizumab plus bevacizumab versus sorafenib | HBV (240, 48%) HCV (108, 22%) Non-viral (153, 31%) |
0.51 (0.32–0.81) 0.43 (0.22–0.87) 0.91 (0.52–1.60) |
0.47 (0.33–0.67) 0.69 (0.39–1.20) 0.71 (0.47–1.08) |
| HIMALAYA191 | Tremelimumab plus durvalumab versus sorafenib | HBV (241, 31%) HCV (214, 27%) Non-viral (327, 42%) |
0.64 (0.48–0.86) 1.06 (0.76–1.49) 0.74 (0.57–0.95) |
NA |
| COSMIC-312 (ref. 204) | Atezolizumab plus cabozantinib versus sorafenib | HBV (190, 29%) HCV (202, 31%) Non-viral (257, 40%) |
0.53 (0.33–0.87) 1.10 (0.72–1.68) 1.18 (0.78–1.79) |
0.46 (0.29–0.73) 0.64 (0.38–1.09) 0.92 (0.60–1.41) |
| ORIENT-32 (ref. 205) | Sintilimab plus IBI305 versus sorafenib | HBV+ (538, 94%) HBV− (33, 6%) |
0.58 (0.43–0.76) 0.80 (0.22–2.87) |
0.56 (0.40–0.76) 0.38 (0.14–1.06) |
| CheckMate 459 (ref. 193) | Nivolumab versus sorafenib | HBV (233, 31%) HCV (173, 23%) Non-viral (336, 45%) |
0.77 (0.56–1.05) 0.71 (0.49–1.01) 0.95 (0.74–1.22) |
NA |
| Immunotherapies — second line | ||||
| KEYNOTE-240 (ref. 194) | Pembrolizumab versus placebo | HBV (101, 24%) HCV (64, 15%) Non-viral (248, 60%) |
0.57 (0.35–0.94) 0.96 (0.48–1.92) 0.88 (0.64–1.20) |
0.70 (0.44–1.13) 0.46 (0.24–0.90) 0.75 (0.56–1.01) |
| Tyrosine kinase inhibitors — first line | ||||
| SHARP184,185 | Sorafenib versus placebo | HBV (111, 18%) HCV (169, 28%) Alcohol (159, 26%) |
0.76 (0.38–1.50) 0.50 (0.32–0.77) 0.76 (0.50–1.16) |
NA |
| Asia–Pacific206,207 | Sorafenib versus placebo | HBV+ (165, 73%) HBV− (61, 27%) |
0.74 (0.51–1.06) 0.57 (0.29–1.13) |
NA |
| REFLECT186 | Lenvatinib versus sorafenib | HBV (479, 50%) HCV (217, 23%) Alcohol (57, 6%) |
0.83 (0.68–1.02) 0.91 (0.66–1.26) 1.03 (0.47–2.28) |
0.62 (0.50–0.75) 0.78 (0.56–1.09) 0.27 (0.11–0.66) |
| Tyrosine kinase inhibitors – second line | ||||
| CELESTIAL188 | Cabozantinib versus placebo | HBV (267, 38%) HCV (168, 24%) Non-viral (272, 38%) |
0.69 (0.51–0.94) 1.11 (0.72–1.71) 0.72 (0.54–0.96) |
0.31 (0.23–0.42) 0.61 (0.42–0.88) 0.48 (0.36–0.63) |
| RESORCE187 | Regorafenib versus placebo | HBV (216, 38%) HCV (119, 21%) Alcohol (145, 25%) |
0.58 (0.41–0.82) 0.79 (0.49–1.26) 0.92 (0.61–1.38 |
0.39 (0.29–0.54) 0.59 (0.39–0.90) 0.53 (0.37–0.77) |
| REACH-2 (ref. 208) | Ramucirumab versus placebo | HBV (107, 37%) HCV (76, 26%) Other (109, 37%) |
0.84 (0.52–1.35) 0.76 (0.44–1.33) 0.63 (0.38–1.06) |
0.43 (0.28–0.68) 0.33 (0.19–0.60) 0.57 (0.35–0.95) |
HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; NA, not available.