Table 3.

Overview of phase-3 first-line clinical trials for systemic therapies in advanced-stage HCC

Trial name (year)	Arms	OS, median (95% CI), months	HR of OS (95% CI)	PFS, median (95% CI), months	HR of PFS (95% CI)	ORR by RECIST 1.1, %
SHARP [102] (2008)	Sorafenib Placebo	10.7 (9.4-13.3) 7.9 (6.8-9.1)	0.69 (0.55-0.87)	5.5 (4.1-6.9) 2.8 (2.7-3.9)	0.58 (0.45-0.74)	2.0 1.0
REFLECT [103] (2018)	Lenvatinib Placebo	13.6 (12.1-14.9) 12.3 (10.4-13.9)	0.92 (0.79-1.06)	7.4 (6.9-8.8) 3.7 (3.6-4.6)	0.66 (0.57-0.77)	18.8 6.5
IMbrave150 [99] (2020)	Atezolizumab plus Bevacizumab Sorafenib	19.2 (17.0-23.7) 13.4 (11.4-16.9)	0.66 (0.52-0.85)	6.9 (5.7-8.6) 4.3 (4.0-5.6)	0.65 (0.53-0.81)	27.3
ORIENT-32 [105] (2021)	Sintilimab plus Bevacizumab biosimilar Sorafenib	Not reached 10.4 (8.5-not reached)	0.57 (0.43-0.75)	4.6 (4.1-5.7) 2.8 (2.7-3.2)	0.56 (0.46-0.70)	21.0 7.0
HIMALAYA [101] (2022)	A: Tremelimumab plus Durvalumab B: Durvalumab C: Sorafenib	16.4 (14.2-19.6) 16.6 (14.1-19.1) 13.8 (12.3-16.1)	A vs. C: 0.78 (0.65-0.92) B vs. C: 0.86 (0.73-1.03)	3.8 (3.7-5.3) 3.7 (3.2-3.8) 4.1 (3.8-5.5)	A vs. C: 0.90 (0.77-1.05) B vs. C: 1.02 (0.88-1.19)	20.1 17.0 5.1
RATIONALE-301 [104] (2022)	Tislelizumab Sorafenib	15.9 14.1	0.85 (0.71-1.02)	2.2 3.6	1.1 (0.92-1.33)	14.3 5.4
COSMIC-312 [106] (2022)	Cabozantinib plus Atezolizumab Sorafenib	15.4 (96%CI 13.7-17.7) 15.5 (96%CI 12.1-not reached)	0.90 (0.69-1.18)	6.8 (99%CI 5.6-8.3) 4.2 (99%CI 2.8-7.0)	0.63 (0.44-0.91)	11 4
LEAP-002 [107] (2022)	Lenvatinib plus Pem-brolizumab Lenvatinib plus placebo	21.2 (19.0-23.6) 19.0 (17.2-21.7)	0.84 (0.71-0.99)	8.2 (6.4-8.4) 8.0 (6.3-8.2)	0.87 (0.73-1.02)	26.1 17.5
CARES-310 [108] (2023)	Camrelizumab plus Rivoceranib Sorafenib	22.1 (19.1-27.2) 15.2 (13.0-18.5)	0.62 (0.49-0.80)	5.6 (5.5-6.3) 3.7 (2.8-3.7)	0.52 (0.41-0.65)	25 6

CI, confidence interval; HR, hazard ratio; ORR, objective response rate; OS, overall survival; PFS, progression-free survival.