. 2018 Feb 17;49(2):107–115. doi: 10.1007/s12029-018-0065-8

Table 1.

Summary of phase 3 trials in HCC

	Investigational vs. comparator arm	OS (investigational)	OS (comparator)	TTP (investigational)	TTP (comparator)	Met primary endpoint?
First line
SHARP [11]	Sorafenib vs. placebo	10.7	7.9	5.5	2.8	Yes
SHARP [11]	Sorafenib vs. placebo	HR 0.69 (95% CI 0.55–0.87), P < 0.001		HR 0.58 (95% CI 0.45–0.74), P < 0.001		Yes
Asia-Pacific study [14]	Sorafenib vs. placebo	6.5	4.2	2.8	1.4	Yes
Asia-Pacific study [14]	Sorafenib vs. placebo	HR 0.68 (95% CI 0.50–0.93), P = 0.014		HR 0.57 (0.42–0.79), P = 0.0005		Yes
Sunitinib trial [15]	Sunitinib vs. sorafenib	7.9	10.2	4.1	3.8	No
Sunitinib trial [15]	Sunitinib vs. sorafenib	HR 1.30 (95% CI 1.13–1.50), P = 0.0014		HR 1.13 (95% CI 0.98–1.31), P = 0.3082		No
BRISK-FL [16]	Brivanib vs. sorafenib	9.5	9.9	4.2	4.1	No
BRISK-FL [16]	Brivanib vs. sorafenib	HR 1.07 (95% CI 0.94–1.23), P = 0.3116		HR 1.01 (95% CI 0.88–1.16), P = 0.8532		No
LIGHT [17]	Linifanib vs. sorafenib	9.1	9.8	5.4	4.0	No
LIGHT [17]	Linifanib vs. sorafenib	HR 1.046 (95% CI 0.896–1.221), NS		HR 0.759 (95% CI 0.643–0.895), P = 0.001		No
SEARCH [18]	Sorafenib + erlotinib vs. sorafenib alone	9.5	8.5	3.2	4.0	No
SEARCH [18]	Sorafenib + erlotinib vs. sorafenib alone	HR 0.929 (95% CI 0.781–1.106), P = 0.408		HR 1.135 (95% CI 0.944–1.366), P = 0.18		No
CALGB 80802 [19]	Sorafenib + doxorubicin vs. sorafenib alone	9.3	10.5	NR	NR	No
CALGB 80802 [19]	Sorafenib + doxorubicin vs. sorafenib alone	HR 1.06 (95% CI 0.8–1.4), NS		NR		No
REFLECT [20]	Lenvatinib vs. sorafenib^a	13.6	12.3	8.9	3.7	Yes
REFLECT [20]	Lenvatinib vs. sorafenib^a	0.92 (0.79–1.06), NR		0.63 (0.53–0.73), NR		Yes
Second line
BRISK-PS [21]	Brivanib vs. placebo	9.4	8.2	4.2	2.7	No
BRISK-PS [21]	Brivanib vs. placebo	HR 0.89 (95% CI 0.69–1.15), P = 0.3307		HR 0.56 (95% CI 0.42–0.76), P < 0.001		No
REACH [22]	Ramucirumab vs. placebo	9.2	7.6	3.5	2.6	No
REACH [22]	Ramucirumab vs. placebo	HR 0.87 (95% CI 0.72–1.05), P = 0.14		HR 0.59 (95% CI 0.49–0.72), P < 0.0001		No
EVOLVE-1 [23]	Everolimus vs. placebo	7.6	7.3	3.0	2.6	No
EVOLVE-1 [23]	Everolimus vs. placebo	HR 1.05 (95% CI 0.86–1.27)		HR 0.93 (95% CI 0.75–1.15), NS		No
RESORCE [24]	Regorafenib vs. placebo	10.6	7.8	3.2	1.5	Yes
RESORCE [24]	Regorafenib vs. placebo	HR 0.63 (95% CI 0.50–0.79), P < 0.0001		HR 0.44 (95% CI 0.36–0.55), P < 0.0001		Yes
JET-HCC [25]	Tivantinib vs. placebo^b	9.9	8.5	NR	NR	No
JET-HCC [25]	Tivantinib vs. placebo^b	HR 0.85 (95% CI 0.59–1.22)		NR		No

Table shows the OS and TTP for the phase 3 trials reporting data in HCC. Medians are given in months

HR hazard ratio, NR not reported, NS not significant, OS overall survival, TTP time to progression

^aNon-inferiority trial design

^bPatients with c-MET high tumors only