Post-immunotherapy second-line strategies for hepatocellular carcinoma: State of the art and ongoing trials

Table 2 Concluded retrospective and prospective studies investigating the efficacy and safety of tyrosine kinase inhibitors as a second-line treatment after progression to first-line immune checkpoint inhibitors

Treatment	Prior treatment	Ref.	Patients (number)	Region	Study design	Child Pugh-A (%)	BCLC-C (%)	MVI (%)	Extrahepatic spread (%)	mPFS (months)	mOS (months)	ORR (%)	DCR (%)	Gr3/4 TRAE (%)
Sora, lenva, cabo	AB	Yoo et al[37]	49	Asia	Retrospective	100	100	38.8		6.1 (lenva); 2.5 (sora)	16.6 (lenva); 11.2 (sora)	15.8 (lenva); 0 (sora)	62.1 (lenva); 63.2 (sora)	16.3
Cabo	ICIs	Storandt et al[38]	26	United States	Retrospective	72				2.1	7.7	4	27	27
Rego vs other mTKIs (sora, lenva, cabo)	AB	Falette-Puisieux et al[39]	82	France	Retrospective	82.9	92.7	37.8	80.5	2.6 (rego); 2.8 (other mTKIs)	15.8 (rego); 7.0 (other mTKIs)			17.2 (rego); 28.3 (other mTKIs)
Sora	AB	Tovoli et al[29]	40	Italy	Retrospective	87.5		42.5	60	3.3	6.9	0	10
Sora vs lenva	AB	Chon et al[40]	126	Korea	Retrospective	72.2	86.6	46	69	3.5 (lenva); 1.8 (sora)	10.3 (lenva); 7.5 (sora)	7.5 (lenva); 5.8 (sora)	67.5 (lenva); 24.4 (sora)	35 (lenva); 38.4 (sora)
Rego	AB	Yoo et al[43]	40	Asia	Prospective	100	97.5			3.5	9.7	10	82.5
Cabo	ICIs	Chan et al[41]	47	Asia	Prospective	100	93.6	30		4.3 (II line); 4.0 (III line)	14.3 (II line); 6.6 (III line)	6.4	83.1
Lenva	AB	Yoo et al[45]	50	Korea	Prospective	100	76	24		5.4	8.6	12	84

cabo: Cabozantinib; sora: Sorafenib; lenva: Lenvatinib; rego: Regorafenib; mTKIs: Multitarget tyrosine kinase inhibitors; AB: Atezolizumab plus bevacizumab; ICIs: Immune checkpoint inhibitors; BCLC: Barcelona Clinic Liver Cancer; MVI: Macrovascular invasion; mOS: Median overall survival; mPFS: Median progression-free survival; DCR: Disease control rates; ORR: Objective response rates; Gr3/4 TRAE: Grade 3/4 treatment related adverse event.