Table 2.

Clinical benefit of ICI according to AFP status

Trial	Phase	Treatment	Target	Notes	Endpoint	AFP, ng/mL	HR(95%CI)	Which emphasizes the benefits of ICI?	PMID
IMbrave150	Phase 3	Atezolizumab + bevacizumab vs sorafenib	PD-L1	First line	PFS	< 400	0.52 (0.34–0.81)	Low AFP	PMID: 32402160
					PFS	> 400	0.68 (0.43–1.08)
					OS	< 400	0.49 (0.36–0.66)	Low AFP
					OS	> 400	0.79 (0.54–1.16)
HIMALAYA	Phase 3	STRIDE vs sorafenib	PD-L1 + CTLA4	First line	OS	< 400	0.82 (0.53–1.05)	High AFP	PMID: 38319892
					OS	> 400	0.64 (0.45–0.91)
		Durvalumab vs sorafenib	PD-L1		OS	< 400	0.78 (0.61–1.01)	High AFP
					OS	> 400	0.73 (0.53–1.03)
RATIONALE-301	Phase 3	Tislezumab vs sorafenib	PD-1	First line	OS	< 400	0.81 (0.64–1.02)	Low AFP	PMID: 37796513
					OS	> 400	0.86 (0.65–1.13)
LEAP-002	Phase 3	Lenvatinib + pembrolizumab vs lenvatinib	PD-1	First line	OS	< 400	0.95 (0.77–1.17)	High AFP	PMID: 38039993
					OS	> 400	0.67 (0.50–0.90)
CheckMate 459	Phase 3	Nivolumab vs sorafenib	PD-1	First line	OS	< 400	0.98 (0.78–1.24)	High AFP	PMID: 34914889
					OS	> 400	0.67 (0.51–0.88)
ORIENT-32	Phase 2–3	Sintilimab + a bevacizumab biosimilar (IBI305) vs sorafenib	PD-1	First line, HBV related	PFS	< 400	0·43 (0·32–0·57)	Low AFP	PMID: 34143971
					PFS	> 400	0·75 (0·55–1·03)
					OS	< 400	0.54 (0.35–0.83)	Low AFP
					OS	> 400	0.59 (0.41–0.85)
KEYNOTE-240	Phase 3	Pembrolizumab vs placebo	PD-1	Sorafenib-treated advanced HCC	PFS	< 200	0.63 (0.46–0.86)	Low AFP	PMID: 37901200
					PFS	> 200	0.83 (0.59–1.16)
					OS	< 200	0.66 (0.49–0.90)	Low AFP
					OS	> 200	0.88 (0.63–1.23)