Table 2.
Results from clinical trials from approved systemic therapies in advanced HCC.
| Clinical Trials in HCC | Phase | Line of Therapy | Arms | Primary Outcome(s) | Median OS (Months) | ORR (%) | Year Approved |
|---|---|---|---|---|---|---|---|
| Multikinase inhibitors and monoclonal antibody against VEGFR2 | |||||||
| SHARP [26] | III | First | Sorafenib (S) Placebo (P) |
OS | S: 10.7 P: 7.9 (HR = 0.69; 95% confidence interval (CI) = 0.55–0.87; p < 0.001) |
S: 43 P: 32 p = 0.002 |
2007 |
| RESORCE [54] | III | Second (post-SOR) | Regorafenib (R) Placebo |
OS | R: 10.6 P: 7.8 (HR = 0.63; 95% CI = 0.50–0.79; p < 0.0001) |
R:11 P: 4 p = 0.0047 |
2017 |
| REFLECT [36] | III | First | Lenvatinib (L), Sorafenib |
OS | L: 13.6 S: 12.3 (HR = 0.92; 95% CI = 0.79–1.06) |
L: 18.8 S: 6.5 p < 0.0001 |
2018 |
| CELESTIAL [55] | III | Second (post-SOR or other) | Cabozantinib (C) Placebo |
OS | C: 10.2 P: 8.0 (HR = 0.76; p < 0.005) |
C:4 P < 1 p = 0.009 |
2019 |
| REACH-2 [56] | III | Second | Ramucirumab (Ra), Placebo (AFP ≥ 400 ng/mL) |
OS | Ra: 8.5 P: 7.3 (HR = 0.71; p < 0.019) |
R:5 P:1 p = 0·1697 |
2019 |
| Immunotherapy (monotherapy) | |||||||
| Keynote-224 [49] | II | Second | Pembrolizumab (Pem) (post-SOR) | ORR |
Pem: 12.9 months (95% CI = 9.7–15.5) |
17 (95% CI = 11–26) |
2018 |
| Checkmate 040 (cohorts 1–3 in dose expansion phase) [46] | I/II | Second | Nivolumab (N) (post-SOR) | ORR |
6 months:83% 9 months:74% |
20 (CI = 15–26) |
2017 |
| MKI with ICI | |||||||
| IMbrave150 (2020) [57] | III | First | Atezolizumab + Bevacizumab (AB), Sorafenib | AB: 19.2 S: 13.4 |
A + B:30 S:11 |
2020 | |
| Dual checkpoint inhibitors | |||||||
| Checkmate 040 (cohort 4) | I/II | Second | Nivolumab + ipilimumab | ORR |
Arm A: 22.8 months (95% CI, 9.4-not reached) Arm B: 12.5 months (95% CI, 7.6–16.4) Arm C: 12.7 months (95% CI, 7.4–33.0) |
ARM A: 32 (95 = CI 20–47) ARM B: 27 (95% CI = 15–41) ARM C: 29 (95% CI = 29 (17–43) |
2020 |
| HIMALAYA [44] | III | First |
Durvalumab + Tremelimumab (STRIDE), Durvalumab (D), Sorafenib |
OS | STRIDE: 16.4 S: 13.8 (HR = 0.78; 96% CI = 0.65–0.92; p = 0.0035) Durvalumab did not demonstrate superiority to sorafenib (p = 0.0674) |
STRIDE:20.1 D: 17 S: 5.1 |
2022 |