Table 3.

Completed Phase III RCTs on targeted drugs for hepatocellular and bile duct cancers.

N	Setting	Intervention	Results	Reference/Clinicaltrials.gov Identifier
1114	Adjuvant HCC	Sorafenib vs. Placebo	RFS HR = 0.940; [95% CI, 0.780–1134]; one-sided p = 0.26	STORM trial [81]
1075	Advanced HCC First-line	Sunitinib vs. Sorafenib	Terminated based on a higher incidence of serious adverse events in the sunitinib and on failure to demonstrate superiority or non-inferiority to sorafenib	NCT00699374
1035	Advanced HCC First-line	Linifanib vs. Sorafenib	OS HR = 1.046; [95% CI, 0.896–1.221]	[82]
870	Intermediate Unresectable HCC	Brivanib vs. Placebo after TACE	HR = 0.90 [95% CI, 0.66–1.23]; log-rank p = 0.5280	[83]
720	Advanced HCC First-line	Sorafenib + Erlotinib vs. Sorafenib + Placebo	OS 9.5 vs. 8.5 months, HR = 0.929; p = 0.408	SEARCH trial [84]
635	Advanced HCC Second-line	ADI-PEG 20 vs. Placebo	OS 7.8 vs. 7.4 months; HR = 1.022 [95% CI, 0.847–1.233]; p = 0.884 PFS 2.6 vs. 2.6 months; HR = 1.175 [95% CI, 0.964–1.432]; p = 0.075	[85]
565	Advanced HCC Second-line	Ramucirumab vs. Placebo after Sorafenib	9.2 vs. 7.6 months; HR = 0.87 [95% CI, 0.72–1.05]; p = 0.14 HR = 0.674; p = 0.0059 with baseline AFP ≥ 400 ng/mL	REACH trial [86]
420	Advanced HCC	Tamoxifen + SOC vs. SOC alone	OS 4.8 [95% CI, 3.6–6] vs. 4.0 months [95% CI, 3.5–4.5]	[87]
395	Advanced HCC Second-line	Brivanib vs. Placebo	OS 9.4 vs. 8.2 months; HR = 0.89 [95.8% CI, 0.69–1.15]; p = 0.3307	BRISK PS trial [88]
230	Adjuvant HCC	CIK vs. Placebo	RFS 44.0 vs. 30.0 months; HR = 0.63; [95% CI, 0.43–0.94]; p = 0.010 OS HR = 0.21 [95% CI, 0.06–0.75]; p = 0.008	[89]
124 *	Advanced BDC	Cis/Gem + Cediranib vs. Cis/Gem + Placebo	PFS HR = 0.93 [95% CI, 0.65–1.35]; p = 0.72	ABC-03 trial [90]

Bile duct cancer (BDC); hazard ratio (HR); hepatocellular carcinoma (HCC); overall survival (OS); progression-free survival (PFS); recurrence-free survival (RFS); standard of care (SOC); trans-arterial chemoembolization (TACE); * Phase 2/3 RCT.