Evidence to Date: Clinical Utility of Tremelimumab in the Treatment of Unresectable Hepatocellular Carcinoma

Figures & data

Table 1 First- and Second-Line Agents for Advanced Hepatocellular Carcinoma

Treatment	Inhibited Molecules	Study Name	Median OS (HR, 95% CI)	Child Pugh A%	Median PFS (HR, 95% CI)
First line Agents
Sorafenib	VEGFR, PDGFR (angiogenesis) MAPK (BRAF)	SHARP (IMbrave150, REFLECT)	10.7–13.4mo (0.69, 0.55–0.87)	95	3.7–4.3mo (NR)
Lenvatinib	VEGFR, PDGFR, FGFR (angiogenesis) KIT, RET	REFLECT	13.6mo (0.92, 0.79–1.06)	99	7.4mo (0.66, 0.57–0.77)
Atezolizumab + Bevacizumab	PDL1 (immune checkpoint) VEGF (angiogenesis)	IMbrave150	19.2mo (0.66, 0.52–0.85)	100	6.9mo (0.65, 0.53–0.81)
Durvalumab+Tremelimumab	PDL1 (immune checkpoint) CTLA4 cytotoxic T lymphocyte-associated antigen-4	HIMALAYA	16.4 (14.2–19.6)	NR	3.8 (3.7–5.3)
Nivolimumab	PDL1 (immune checkpoint)	CHECKMATE 040	22 mo	NR	NR
Second line agents
Regorafenib	VEGFR, PDGFR (angiogenesis)MAPK (BRAF)	RESORCE	10.6mo (0.63, 0.5–0.79)	98	3.1mo (0.46, 0.37–0.56)
Cabozantinib	MET (proliferation)VEGFR (angiogenesis)RET	CELESTIAL	10.2mo (0.76, 0.63–0.92)	98	5.2mo (0.44, 0.36–0.52)
Pembrolizumab	PD1 (immune checkpoint)	KEYNOTE 240	13.9mo (0.78, 0.61–1)	100	3mo (0.78, 0.61–0.99)
Pembrolizumab	PD1 (immune checkpoint)	KEYNOTE 224	13.2 mo	94	4.9 mo
Ramucirumab (AFP > 400 ng/mL)	VEGFR2	REACH −2	8.5 mo (0.71,0.53–0.95)	100	2.8 mo (0.63,0.52–0.75)

Abbreviations: AFP, alpha-fetoprotein; BCLC, Barcelona Clinic Liver Cancer stage; CI, confidence interval; CTLA4, cytotoxic T-lymphocyte antigen 4; FGFR, fibroblast growth factor receptor; HCC, hepatocellular carcinoma; mo, months; NR, not reported; OS, overall survival; PD1, programmed cell death protein 1; PD-L1, programmed death ligand 1; PDGFR, platelet-derived growth factor receptor; PFS, progression-free survival; VEGFR, vascular endothelial growth-factor receptor.

Figure 1 Management algorithm for advanced hepatocellular carcinoma.

Figure 2 Past and ongoing trials examining tremelimumab combination therapies in patients with hepatocellular carcinoma.

Abbreviations: Mo, months; OS, overall survival; TACE, transarterial chemoembolization; Y-90, yttrium-90.