Table 3.

Clinical trials of FDA-approved treatments in patients with advanced HCC.

	Median Age (y) (range)	Overall Survival	Time to Progression	Objective Response Rate	Median Duration of Treatment	Survival in Older adults
First-line
Sorafenib vs Placebo76	64.9 (n/a) vs 66.3 (n/a)	10.7 mo vs 7.9 mo (HR 0.69; 95% CI: 0.55–0.87; p<0.001)	5.5 mo vs 2.8 mo (p<0.001)	n/a	5.3 mo	n/a
Lenvatinib vs Sorafenib70 (non-inferiority)	63 (20–88) vs 62 (22–88) [65y- <75y: 30%; 75+: 13%]	13.6 mo vs 12.3 mo (HR 0.92; 95% CI: 0.79–1.06; p n/a)	8.9 mo vs 3.7 mo (HR 0.63; 95% CI: 0.53 –0.73; p<0.0001)	24.1 % vs 9.2% (p<0.0001)	5.7 mo	mOS: 14.6 mo vs 13.4 mo (HR 0.84; 95% CI: 0.661.07)
Second-line
Regorafenib vs placebo71 (tolerated prior sorafenib > 20 days at > 400 mg/day)	64 (54–71) vs 62 (55–68)	10.6 mo vs 7.8 mo (HR 0.63; 95% CI: 0.500.79; p<0.0001)	3.1 mo vs 1.5 mo (HR 0.46; 95% CI: 0.37–0.56; p<0.0001	11% vs 4% (p=0.0047)	3.6 mo	mOS: HR was 0.74 (95% CI: 0.490.87)
Cabozantinib vs placebo72 (2nd and 3d line)	64 (22–86) vs 64 (24–86)	10.2 vs 8 mo (HR 0.76; 95% CI: 0.63–0.92; p=0.005)	5.2 mo vs 1.9 mo (HR 0.44; 95% CI: 0.36–0.52; p<0.001)	4% vs <1% (p=0.009)	3.8 mo	mOS: HR 0.46 (95% CI: 0.350.59)
Ramucirumab vs placebo94 (AFP >400 ng/mL)	64 (58–73) vs 64 (56–71)	8.5 mo vs 7.3 mo (HR 0.710; 95% CI: 0.531–0.949; p=0.0199)	2.8 mo vs 1.6 mo (HR 0.452; 95% CI: 0.339–0.603; p<.0001)	5% vs 1% (p=0.1697)	12 weeks	mOS: HR 0.641 (0.4290.957)
Nivolumab73	Expansion phase: 64 (56–70) [65+: 47%]	Not reached; 6-mo OS rate was 83%	4.1 mo (95% CI: 3.75.5)	20%	n/a	n/a
Pembrolizumab vs placebo88	(18–91) vs (23–89)	13.9 mo vs 10.6 mo (HR 0.781; CI 95%: 0.6110.998; p=0.0238)	3.0 mo vs 2.8 mo (HR 0.718; CI 95%: 0.5700.904; p=0.0022)	18.3% vs 4.4% (p=0.00007)	n/a	n/a

Mo = months, y = years, HR = hazard ratio, CI = Confidence interval, vs = versus, n/a = not available.