Microbiome dysbiosis and immune checkpoint inhibitors: Dual targets in Hepatocellular carcinoma management

Table 1 Immune checkpoint inhibitors efficacy in hepatocellular carcinoma

Study name	Regimen	Line of therapy	No. of patients	ORR (%)	mPFS (months)	mOS (months)	Findings
ICI single therapy
CheckMate 459[7,36]	Nivolumab vs Sorafenib	1st line	743	15	3.7 vs 3.8	16.4 vs 14.7	HR death 0.85 (95%CI: 0.72-1.00; P = 0.0522)
Keynote-224[9]	Pembrolizumab	2nd line	104	17	4.9	13.2	Durable anti-tumour activity and improvement in BOR. CR increased vs the primary analysis (3.8% vs 1.0%)
Keynote-240[8]	Pembrolizumab vs Placebo	2nd line	413	18 vs 4	3.0 vs 2.8	13.9 vs 10.6	Did not met the threshold HR of 0.781 (95%CI: 0.611 to 0.998; P = 0.0238) and 0.775 (95%CI: 0.609-0.987; P = 0.0186) for OS and PFS
Keynote-394[37]	Pembrolizumab vs Placebo	2nd line (Asian)	453	13.9 vs 1.3	2.6 vs 2.3	14.6 vs 13.0	Significance OS/PFS benefit (HR = 0.79; 95%CI: 0.63-0.99; P = 0.018)
HIMALAYA[38]	STRIDE (Durva + Tremeli) vs Sorafenib	1st line	1171	20.1	3.78 vs 4.07	16.4 vs 13.8	Significance OS (HR = 0.78; 96%CI: 0.65–0.92; P = 0.0035)
RATIONALE-301[39]	Tislelizumab vs Sorafenib	1st line	674	14.3 vs 5.4	2.3 vs 3.3	15.9 vs 14.1	OS non-inferior (HR = 0.85; 95%CI: 0.712-1.019)
Sangro et al[40] 2013	Tremelimumab	2nd line	21	17.6	NA	8.2	Median TTP 6.48 months (95%CI: 3.95–9.14)
ICI combination therapies
CheckMate 040[47]	Nivolumab + Ipilimumab	2nd line	148	32-31	2.96-4.0	22.8-12.5	Arm A, the 12-mOS rate was 61% (95%CI: 0.46-0.73)
CheckMate 9DW[46]	Nivolumab + Ipilimumab vs Sorafenib/Lenvatinib	1st line	1084	36 vs 13	9.1 vs 9.2	23.7 vs 20.6	Significantly improve OS (HR = 0.79, 95%CI: 0.65-0.96; P = 0.018)
IMbrave150[43]	Atezolizumab + Bevacizumab vs Sorafenib	1st line	336 vs 165	27.3 vs 11.9	6.8 vs 4.3	19.1 vs 13.4	HR death 0.58 (95%CI 0.42–0.79; P < 0.001)
AMETHISTA[44]	Atezolizumab + Bevacizumab (Single arm)	1st line	152	26.9	8.51	18.23	TEAEs in 28.9%
COSMIC-312[45]	Atezolizumab Cabozantinib vs sorafenib	1st line	837	NA	6.8 vs 4.2	15.4 vs 15.5	HR death 0.63 (95%CI: 0.44-0.91, P = 0.0012)

HR: Hazard risk; BOR: Best overall response; CR: Complete response; OS: Overall survival; PFS: Progression-free survival; TTP: Time to progression; TEAE: Treatment-emergent adverse events.