Meta-Analysis
Copyright ©The Author(s) 2021.
World J Gastroenterol. May 21, 2021; 27(19): 2415-2433
Published online May 21, 2021. doi: 10.3748/wjg.v27.i19.2415
Table 1 Details of included studies
Ref.
Year
Experimental arm(s)
Comparator arm
Primary endpoint
Analysis timing
Survival outcomes, mo
Yen et al[47]2018NintedanibSorafenibTTPPFS: Final; OS: FinalPFS: 2.7 vs 3.7; OS: 10.2 vs 1.1
Ciuleanu et al[48]2016Mapatumumab + sorafenibPlacebo + sorafenibTTPPFS: Final; OS: FinalPFS: 3.2 vs 4.3; OS: 10.0 vs 10.1
Finn et al[11]2020Atezolizumab + bevacizumabSorafenibOS and PFSPFS: Final; OS: FinalPFS: 6.8 vs 4.3; OS: NE vs 13.2
Abou-Alfa et al[49]2010Doxorubicin + sorafenibDoxorubicin + placeboTTPPFS: Final; OS: FinalPFS: 6.0 vs 2.7; OS: 13.7 vs 6.5
Cheng et al[50]2016DovitinibSorafenibOS and TTPTTP: Final; OS: FinalTTP: 4.1 vs 4.1; OS: 8.0 vs 8.4
Cheng et al[28]2015Tigatuzumab (6 + 2) + sorafenib; Tigatuzumab (6 + 6) + sorafenibSorafenibTTPTTP: Final; OS: FinalTTP: 3.0 vs 3.9 vs 2.8; OS: 8.2 vs 12.2 vs 8.2
Hsu et al[51]2012Vandetanib 300 mg/d; Vandetanib 100 mg/dPlaceboTumor stabilization ratePFS: Final; OS: FinalPFS: 1.1 vs 0.7 vs 1.0; OS: 6.0 vs 5.8 vs 4.3
Johnson et al[22]2013SorafenibBrivanibOSPFS: No; OS: FinalPFS: 4.1 vs 4.2; OS: 9.9 vs 9.5
Cainap et al[24]2015LinifanibSorafenibOSPFS: Final; OS: FinalPFS: 4.2 vs 2.9; OS: 9.1 vs 9.8
Kudo et al[10]2018LenvatinibSorafenibOSPFS: No; OS: FinalPFS: 7.4 vs 3.7; OS: 13.6 vs 12.3
Yau et al[23]2019NivolumabSorafenibOSPFS: Final; OS: FinalPFS: 3.7 vs 3.8; OS: 16.4 vs 14.7
Cheng et al[29]2013SunitinibSorafenibOSPFS: Final;OS: FinalPFS: 3.6 vs 3.0; OS: 7.9 vs 10.2
Zhu et al[26]2015Sorafenib + erlotinibSorafenib + placeboOSTTP: Final; OS: FinalTTP: 3.2 vs 4.0; OS: 9.5 vs 8.5
Llovet et al[52]2008SorafenibPlaceboOS and TTPTTP: Final; OS: FinalTSP: 5.5 vs 2.8; OS: 10.7 vs 7.9
Cheng et al[25]2009SorafenibPlacebo-TTP: Final; OS: FinalTTP: 2.8 vs 1.4; OS: 6.5 vs 4.2
Palmer et al[53]2018NintedanibSorafenibTTPPFS: Final; OS: FinalPFS: 5.3 vs 3.9; OS: 11.9 vs 11.4
Thomas et al[54]2018Bevacizumab + erlotinibSorafenibOSPFS: No; OS: FinalPFS: 4.4 vs 2.8; OS: 8.6 vs 8.6
Abou-Alfa et al[55]2019Sorafenib + doxorubicinSorafenibOSPFS: Final; OS: FinalPFS: 4.0 vs 3.7; OS: 9.3 vs. 9.4
Tak et al[27]2018SorafenibSorafenib + resminostatTTPTTP: Final; OS: FinalTTP: 2.8 vs 2.8; OS: 14.1 vs 11.8
Jouve et al[56]2019Sorafenib + pravastatinSorafenibOSPFS: Final; OS: FinalPFS: 5.0 vs 5.4; OS: 10.7 vs 10.5
Lee et al[57]2016AEG35156 + sorafenibSorafenibPFSPFS: Final; OS: FinalPFS: 4.0 vs 2.6; OS: 6.5 vs 5.4
Assenat et al[58]2019Sorafenib + GEMOXSorafenibPFSPFS: Final; OS: FinalPFS: 6.2 vs 4.6; OS:13.5 vs 14.8
Azim et al[59]2018Sorafenib + tegafur–uracilSorafenibTTPPFS: Final; OS: FinalPFS: 6.0 vs 6.0; OS: 8.2 vs 10.5
Koeberle et al[60]2016SorafenibSorafenib + everolimusPFSPFS: Final; OS: FinalPFS: 6.6 vs 5.7; OS: 10.0 vs 12
Bi et al[17]2020DonafinibSorafenibOSPFS: Final; OS: FinalPFS: 3.7 vs 3.6; OS: 21.1 vs 10.3
Qin et al[61]2013FOLFOX4DoxorubicinOSPFS: Final; OS: FinalPFS: 2.9 vs 1.8; OS: 6.4 vs 5.0
Yeo et al[62]2005DoxorubicinPIAFOSPFS: No; OS: FinalOS: 6.8 vs 8.7
Table 2 Patient characteristics in the included studies
Ref.
Year
Treatments
n
Age, median
Males, %
ECOG 0/1–2, %
Extrahepatic disease, %
Yen et al[47]2018Nintedanib63589155.6/44.568.3
Sorafenib32628156.3/43.868.3
Ciuleanu et al[48]2016Mapatumumab + sorafenib50605236.0/64.066.0
Placebo + sorafenib51617733.3/66.649.0
Finn et al[11]2020Atezolizumab + bevacizumab336648262.0/38.063.0
Sorafenib165668362.0/38.056.0
Abou-Alfa et al[49]2010Doxorubicin + sorafenib476666-51.1
Doxorubicin + placebo496586-79.6
Cheng et al[50]2016Dovitinib82568963.0/37.0-
Sorafenib83568164.0/35.0-
Cheng et al[28]2015Tigatuzumab (6 + 2) + sorafenib53638560.4/39.6-
Tigatuzumab (6 + 6) + sorafenib54638357.4/42.6-
Sorafenib55668054.5/45.5-
Hsu et al[51]2012Vandetanib 300 mg/d195595--
Vandetanib 100 mg/d256168--
Placebo235687--
Johnson et al[22]2013Sorafenib578608461.0/39.062.0
Brivanib577618464.0/36.063.0
Cainap et al[24]2015Linifanib514598662.8/37.259.7
Sorafenib521608466.2/33.856.8
Kudo et al[10]2018Lenvatinib4786385--
Sorafenib4766284--
Yau et al[23]2019Nivolumab3716585--
Sorafenib3726585--
Cheng et al[29]2013Sunitinib530598252.5/46.878.9
Sorafenib544598452.9/46.776.3
Zhu et al[26]2015Sorafenib + erlotinib362608261.3/38.756.6
Sorafenib + placebo358618060.3/39.761.2
Llovet et al[52]2008Sorafenib299658754.0/46.053.0
Placebo303668754.0/46.050.0
Cheng et al[25]2009Sorafenib150518525.3/74.668.7
Placebo76528727.6/72.468.4
Palmer et al[53]2018Nintedanib62667751.6/48.464.5
Sorafenib31648458.1/33.067.7
Thomas et al[54]2018Bevacizumab + erlotinib4761NR32.0/68.040.0
Sorafenib4361NR40.0/60.025.0
Abou-Alfa et al[55]2019Sorafenib + doxorubicin180628536.1/63.9-
Sorafenib176628739.8/60.2-
Tak et al[27]2018Sorafenib846287-56.0
Sorafenib + resminostat866580-51.8
Jouve et al[56]2019Sorafenib + pravastatin1626896-29.0
Sorafenib1616888-30.4
Lee et al[57]2016AEG35156 + sorafenib3161873.2/96.8-
Sorafenib17548811.8/88.3-
Assenat et al[58]2019Sorafenib + GEMOX396286-77.0
Sorafenib446592-61.0
Azim et al[59]2018Sorafenib + tegafur–uracil36598669.4/30.652.8
Sorafenib38599065.8/34.247.4
Koeberle et al[60]2016Sorafenib46658772.0/28.057.0
Sorafenib + everolimus59668159.0/41.054.0
Bi et al[17]2020Donafinib328538661.3/38.7-
Sorafenib331538866.8/33.2-
Qin et al[61]2013FOLFOX41845090--
Doxorubicin1874987--
Yeo et al[62]2005Doxorubicin94549087.2/12.8-
PIAF94499392.6/7.4-