Immunotherapy for recurrent hepatocellular carcinoma

Table 1 Immunotherapy regimens for first-line use in patients with advanced hepatocellular carcinoma with no prior systemic therapy

Immunotherapy regimen	IMBRAVE150 (NCT03434379)	HIMALAYA (NCT03298451)
Drugs	Atezolizumab, Bevacizumab	Durvalumab, Tremelimumab
Drug class combination	PD-L1 inhibitor, VEGF inhibitor	PD-1 inhibitor, CTLA-4 inhibitor
Study population	Child-Pugh A, ECOG score 0/1, no prior systemic therapy	Child-Pugh A, ECOG score 0/1, BCLC B or C, no prior systemic therapy
Key difference	Portal vein thrombosis patients included	Portal vein thrombosis patients excluded
EGD required?	Yes	No
Overall survival	19.2 mo (95%CI: 17.0-23.7)	16.4 mo (95%CI: 14.2-19.6)
Median progression free survival	6.8 mo (95%CI: 5.7-8.3) vs 4.3 (95%CI: 4.0-5.6)	3.8 mo (95%CI: 3.7-5.3)
Overall response rate	27.3% (95%CI: 22.5-32.5)	STRIDE arm: 20.1%
Long-term survival data	Not available	Available

BCLC: Barcelona Clinic Liver Cancer; CI: Confidence interval; CTLA-4: Cytotoxic T lymphocyte associated protein-4; ECOG: Eastern Cooperative Oncology Group; EGD: Esophagogastroduodenoscopy; FDA: Food and Drug Administration; PD-1: Programmed cell death protein-1; PD-L1: Programmed death- ligand 1; STRIDE: Single Tremelimumab Regular Interval Durvalumab; VEGF: Vascular endothelial growth factor.

Table 2 Current Food and Drug Administration-approved immunotherapy agents in second-line use post-progression on sorafenib in advanced hepatocellular carcinoma

Immunotherapy agent	Checkmate 040 (NCT01658878)	Keynote 224 (NCT02702414)
Drugs	Ipilimumab, nivolumab	Pembrolizumab
Drug class combination	CTLA-4 inhibitor, PD-1 inhibitor	PD-1 inhibitor
Study population	Child-Pugh A, ECOG score 0/1, prior systemic therapy with sorafenib or intolerance to sorafenib	Child-Pugh A, ECOG score 0/1, prior systemic therapy with sorafenib or intolerance to sorafenib
Overall survival	22.8mo (95%CI: 9.4-not reached)	12.9 mo (95%CI: 9.7-15.5)
Median progression free survival	3.9 mo (95%CI: 2.6-8.3)	4.9 mo (95%CI: 3.4-7.2)
Overall response rate	32%	18%
Most common treatment related AE	Rash, hepatitis, hypothyroidism	Hypothyroidism, hepatitis, adrenal insufficiency
Child-Pugh score B group studied	No data available	Retrospective data available
FDA approval	Yes	Yes

CI: Confidence interval; CTLA-4: Cytotoxic T lymphocyte associated protein-4; ECOG: Eastern cooperative oncology group; FDA: Food and drug administration; PD-1: Programmed cell death protein- 1.

Table 3 Possible treatment regimens for patients with advanced hepatocellular carcinoma who have recurred on local therapy

Patient group	Treatment	Status
Advanced HCC patients with no prior systemic therapy	Atezolizumab + bevacizumab	FDA approved for first-line use (no contraindications to atezolizumab/bevacizumab or both)
	Durvalumab + tremelimumab	Contraindications to atezolizumab or bevacizumab or both; FDA approved for first-line use
	Single agent immunotherapy	Poor ECOG 3-4
Advanced HCC with prior systemic therapy with TKIs like sorafenib or lenvatinib	Ipilimumab + nivolumab	FDA approved for second-line use
	Pembrolizumab	FDA approved for second-line use; High risk subgroups: Asian patients, poor ECOG
	Atezolizumab + bevacizumab	Warrants further evaluation
	Durvalumab + tremelimumab
	Clinical trials
HCC patients with prior IO based systemic therapy	Partner switching from currently available first-line options	Using drugs with different mechanism of action in comparison to first line IO therapy
	Pembrolizumab	Warrants further evaluation
	Ipilimumab + nivolumab
	Clinical trials

ECOG: Eastern cooperative oncology group; FDA: Food and drug administration; HCC: Hepatocellular carcinoma; IO: Immunotherapy; TKI: Tyrosine kinase inhibitor.