Difference between revisions of "Staging page"

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[[#top|Back to Top]]
 
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{{#lst:Section editor transclusions|giei}}
 
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''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Hepatocellular_carcinoma_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Hepatocellular carcinoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''.
 
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{| class="wikitable" style="float:right; margin-right: 5px;"
 
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|-
 
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
 
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
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|}
 
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{{TOC limit|limit=3}}
 
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=Guidelines=
 
−
==AASLD==
 
−
*'''2018:''' Marrero et al. [https://doi.org/10.1002/hep.29913 Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases]
 
−
==[http://www.asco.org/ ASCO]==
 
−
*'''2020:''' Gordan et al. [https://doi.org/10.1200/jco.20.02672 Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline]
 
−
==[http://www.esmo.org/ ESMO]==
 
−
*'''2018:''' Vogel et al. [https://www.esmo.org/Guidelines/Gastrointestinal-Cancers/Hepatocellular-Carcinoma Hepatocellular Carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 
−
===Older===
 
−
*'''2012:''' Verslype et al. [http://annonc.oxfordjournals.org/content/23/suppl_7/vii41.full.pdf+html Hepatocellular carcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up.] [https://pubmed.ncbi.nlm.nih.gov/22997453 PubMed]
 
−
==[https://www.nccn.org/ NCCN]==
 
−
*[https://www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf NCCN Guidelines - Hepatobiliary Cancers]
 
−
==TOS/ESMO==
 
−
*'''2020:''' Chen et al. [https://doi.org/10.1016/j.annonc.2019.12.001 Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with intermediate and advanced/relapsed hepatocellular carcinoma: a TOS–ESMO initiative endorsed by CSCO, ISMPO, JSMO, KSMO, MOS and SSO]
 
−
=Local therapy=
 
−
==Axitinib & TACE {{#subobject:ffb7ae|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:48d017|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/full/10.1002/cncr.30825 Chan et al. 2017 (HCC028)]
 
−
|2011-2014
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Axitinib (Inlyta)]] 5 mg PO twice per day, held before and after TACE
 
−
====Chemotherapy====
 
−
*[[TACE]]
 
−
</div></div>
 
−
===References===
 
−
#'''HCC028:''' Chan SL, Yeo W, Mo F, Chan AWH, Koh J, Li L, Hui EP, Chong CCN, Lai PBS, Mok TSK, Yu SCH. A phase 2 study of the efficacy and biomarker on the combination of transarterial chemoembolization and axitinib in the treatment of inoperable hepatocellular carcinoma. Cancer. 2017 Oct 15;123(20):3977-3985. Epub 2017 Jun 22. [https://doi.org/full/10.1002/cncr.30825 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28640364 PubMed] NCT01352728
 
−
==DEB-TACE {{#subobject:7acb7b|Regimen=1}}==
 
−
DEB-TACE: '''<u>D</u>'''rug-'''<u>E</u>'''luting '''<u>B</u>'''ead '''<u>T</u>'''rans-'''<u>A</u>'''rterial '''<u>C</u>'''hemo-'''<u>E</u>'''mbolization
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:35a248|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966514/ Brown et al. 2016 (MSK 07-099)]
 
−
|2007-2012
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|Bland embolization
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1016/S2468-1253(17)30156-5 Meyer et al. 2017 (TACE2)]
 
−
|2010-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|DEB-TACE & Sorafenib
 
−
| style="background-color:#ffffbf" |Did not meet primary outcome of PFS
 
−
|-
 
−
|}
 
−
''Note: TACE2 assessed the addition of concurrent sorafenib to DEB-TACE.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Eligibility criteria====
 
−
*TACE2: Child-Pugh A liver disease, and ECOG PS 0 or 1
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[TACE]] with drug-eluting beads loaded with [[Doxorubicin (Adriamycin)]] 150 mg
 
−
'''One treatment'''
 
−
</div></div>
 
−
===References===
 
−
#'''MSK 07-099:''' Brown KT, Do RK, Gonen M, Covey AM, Getrajdman GI, Sofocleous CT, Jarnagin WR, D'Angelica MI, Allen PJ, Erinjeri JP, Brody LA, O'Neill GP, Johnson KN, Garcia AR, Beattie C, Zhao B, Solomon SB, Schwartz LH, DeMatteo R, Abou-Alfa GK. Randomized trial of hepatic artery embolization for hepatocellular carcinoma using doxorubicin-eluting microspheres compared with embolization with microspheres alone. J Clin Oncol. 2016 Jun 10;34(17):2046-53. Epub 2016 Feb 1. [https://doi.org/10.1200/JCO.2015.64.0821 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966514/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26834067 PubMed] NCT00539643
 
−
#'''TACE2:''' Meyer T, Fox R, Ma YT, Ross PJ, James MW, Sturgess R, Stubbs C, Stocken DD, Wall L, Watkinson A, Hacking N, Evans TRJ, Collins P, Hubner RA, Cunningham D, Primrose JN, Johnson PJ, Palmer DH. Sorafenib in combination with transarterial chemoembolization in patients with unresectable hepatocellular carcimoma (TACE2): a randomized placebo-controlled, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2017 Aug;2(8):565-575. Epub 2017 Jun 23. [https://doi.org/10.1016/S2468-1253(17)30156-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28648803 PubMed] NCT01324076
 
−
==Radioembolization {{#subobject:4f040c|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:ea43b3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.76.0892 Chow et al. 2018 (SIRveNIB)]
 
−
|2010-2016
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|[[#Sorafenib_monotherapy|Sorafenib]]
 
−
| style="background-color:#ffffbf" |Did not meet primary outcome of OS
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(17)30683-6 Vilgrain et al. 2017 (SARAH)]
 
−
|2011-2015
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|[[#Sorafenib_monotherapy|Sorafenib]]
 
−
| style="background-color:#ffffbf" |Did not meet primary outcome of OS
 
−
|}
 
−
====Synopsis====
 
−
*SARAH was a multicenter European study that also included patients without two unsuccessful rounds of TACE. Primary endpoint of improved OS was not met; Y90 was associated with higher ORR, lower DCR, fewer AE, and similar survival. Additional post-hoc analysis showed patients who received Y90 at > or equal to 100 Gy may derive a meaningful response as compared to sorafenib.
 
−
*SIRveNIB was a multicenter Asian study randomized newly diagnosed patients with locally advanced inoperable HCC to a single injection of Y90 or sorafenib until progressive disease or unacceptable toxicity. Primary endpoint of improved OS was not met; Y90 was associated with higher ORR, few SAE, and similar OS, similar OS and DCR.
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Radiotherapy====
 
−
*[[Brachytherapy|Selective internal radiotherapy (SIRT) with yttrium-90 resin microspheres]]
 
−
</div></div>
 
−
===References===
 
−
#'''SARAH:''' Vilgrain V, Pereira H, Assenat E, Guiu B, Ilonca AD, Pageaux GP, Sibert A, Bouattour M, Lebtahi R, Allaham W, Barraud H, Laurent V, Mathias E, Bronowicki JP, Tasu JP, Perdrisot R, Silvain C, Gerolami R, Mundler O, Seitz JF, Vidal V, Aubé C, Oberti F, Couturier O, Brenot-Rossi I, Raoul JL, Sarran A, Costentin C, Itti E, Luciani A, Adam R, Lewin M, Samuel D, Ronot M, Dinut A, Castera L, Chatellier G; SARAH Trial Group. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomized controlled phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1624-1636. Epub 2017 Oct 26. [https://doi.org/10.1016/S1470-2045(17)30683-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29107679 PubMed] NCT01482442
 
−
##'''Update: Abstract:''' Hawkins NS, Ross PJ, Palmer DH, Chatellier G, Pereira H, Vilgrain V. Overall survival of patients with hepatocellular carcinoma receiving sorafenib versus selective internal radiation therapy with predicted osimetry in the SARAH trial. Annals of Oncology. 2019 Sept; 30 (suppl_5): v253-v324. Epub 2019 Sept 29. [https://academic.oup.com/annonc/article/30/Supplement_5/mdz247.063/5576666 link to original article]
 
−
<!-- # '''Abstract:''' Chow PHW, Gandhi M. Phase III multi-centre open-label randomized controlled trial of selective internal radiation therapy (SIRT) versus sorafenib in locally advanced hepatocellular carcinoma: The SIRveNIB study (abstract). J Clin Oncol 35, 2017 suppl; abstr 4002). [http://abstracts.asco.org/199/AbstView_199_187604.html link to abstract] -->
 
−
#'''SIRveNIB:''' Chow PKH, Gandhi M, Tan SB, Khin MW, Khasbazar A, Ong J, Choo SP, Cheow PC, Chotipanich C, Lim K, Lesmana LA, Manuaba TW, Yoong BK, Raj A, Law CS, Cua IHY, Lobo RR, Teh CSC, Kim YH, Jong YW, Han HS, Bae SH, Yoon HK, Lee RC, Hung CF, Peng CY, Liang PC, Bartlett A, Kok KYY, Thng CH, Low AS, Goh ASW, Tay KH, Lo RHG, Goh BKP, Ng DCE, Lekurwale G, Liew WM, Gebski V, Mak KSW, Soo KC; Asia-Pacific Hepatocellular Carcinoma Trials Group. SIRveNIB: selective internal radiation therapy versus sorafenib in Asia-Pacific patients with hepatocellular carcinoma. J Clin Oncol. 2018 Jul 1;36(19):1913-1921. Epub 2018 Mar 2. [https://doi.org/10.1200/JCO.2017.76.0892 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29498924 PubMed] NCT01135056
 
−
==TACE monotherapy {{#subobject:f96a1b|Regimen=1}}==
 
−
TACE: '''<u>T</u>'''rans-'''<u>A</u>'''rterial '''<u>C</u>'''hemo-'''<u>E</u>'''mbolization
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:93050b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM199505113321903 Trinchet et al. 1995]
 
−
|1990-1992
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Hepatocellular_carcinoma_-_null_regimens#Best_supportive_care|Best supportive care]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(02)08649-X Llovet et al. 2002]
 
−
|1996-2000
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Hepatocellular_carcinoma_-_null_regimens#Best_supportive_care|Best supportive care]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://www.journal-of-hepatology.eu/article/S0168-8278(09)00588-1 Okusaka et al. 2009]
 
−
|1999-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|TAI
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(11)00324-8 Kudo et al. 2011 (Bayer 11721)]
 
−
|2006-2009
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5846877/ Ikeda et al. 2017]
 
−
|2008-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|TACE with Miriplatin
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep.27290 Kudo et al. 2014 (BRISK TA)]
 
−
|2009-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#TACE_.26_Brivanib_77|TACE & Brivanib]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1016/S2468-1253(17)30290-X Kudo et al. 2017 (ORIENTAL)]
 
−
|2010-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#TACE_.26_Orantinib_77|TACE & Orantinib]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
====Synopsis====
 
−
*Bayer 11721 was a Japanese and Korean study including patients with Child-Pugh A cirrhosis with a primary endpoint of TTP, and secondary endpoint of OS. More than 50% of patients started sorafenib after 9 weeks post TACE. 73% of patients had dose reductions, and 91% of patients had dose interruptions.
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[TACE]]
 
−
'''1 or more treatments'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Bayer 11721: [[Hepatocellular_carcinoma_-_null_regimens#Placebo|Placebo]] versus sorafenib
 
−
</div></div>
 
−
===References===
 
−
#Trinchet JC, Abou Rached A, Beaugrand M, Mathieu D, Chevret S, Chastang C; Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire. A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma. N Engl J Med. 1995 May 11;332(19):1256-61. [https://doi.org/10.1056/NEJM199505113321903 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7708069 PubMed]
 
−
#Llovet JM, Real MI, Montaña X, Planas R, Coll S, Aponte J, Ayuso C, Sala M, Muchart J, Solà R, Rodés J, Bruix J; Barcelona Liver Cancer Group. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002 May 18;359(9319):1734-9. [https://doi.org/10.1016/S0140-6736(02)08649-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/12049862 PubMed]
 
−
#Okusaka T, Kasugai H, Shioyama Y, Tanaka K, Kudo M, Saisho H, Osaki Y, Sata M, Fujiyama S, Kumada T, Sato K, Yamamoto S, Hinotsu S, Sato T. Transarterial chemotherapy alone versus transarterial chemoembolization for hepatocellular carcinoma: a randomized phase III trial. J Hepatol. 2009 Dec;51(6):1030-6. Epub 2009 Oct 1. [https://www.journal-of-hepatology.eu/article/S0168-8278(09)00588-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19864035 PubMed]
 
−
#'''Bayer 11721:''' Kudo M, Imanaka K, Chida N, Nakachi K, Tak WY, Takayama T, Yoon JH, Hori T, Kumada H, Hayashi N, Kaneko S, Tsubouchi H, Suh DJ, Furuse J, Okusaka T, Tanaka K, Matsui O, Wada M, Yamaguchi I, Ohya T, Meinhardt G, Okita K. Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma. Eur J Cancer. 2011 Sep;47(14):2117-27. [https://www.ejcancer.com/article/S0959-8049(11)00324-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21664811 PubMed] NCT00494299
 
−
#'''BRISK TA:''' Kudo M, Han G, Finn RS, Poon RT, Blanc JF, Yan L, Yang J, Lu L, Tak WY, Yu X, Lee JH, Lin SM, Wu C, Tanwandee T, Shao G, Walters IB, Dela Cruz C, Poulart V, Wang JH. Brivanib as adjuvant therapy to transarterial chemoembolization in patients with hepatocellular carcinoma: A randomized phase III trial. Hepatology. 2014 Nov;60(5):1697-707. Epub 2014 Sep 29. [https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep.27290 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24996197 PubMed] NCT00908752
 
−
#Ikeda M, Kudo M, Aikata H, Nagamatsu H, Ishii H, Yokosuka O, Torimura T, Morimoto M, Ikeda K, Kumada H, Sato T, Kawai I, Yamashita T, Horio H, Okusaka T; Miriplatin TACE Study Group. Transarterial chemoembolization with miriplatin vs epirubicin for unresectable hepatocellular carcinoma: a phase III randomized trial. J Gastroenterol. 2018 Feb;53(2):281-290. Epub 2017 Aug 1. [https://doi.org/10.1007/s00535-017-1374-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5846877/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28766016 PubMed] JapicCTI-080632
 
−
#'''ORIENTAL:''' Kudo M, Cheng AL, Park JW, Park JH, Liang PC, Hidaka H, Izumi N, Heo J, Lee YJ, Sheen IS, Chiu CF, Arioka H, Morita S, Arai Y. Orantinib versus placebo combined with transcatheter arterial chemoembolisation in patients with unresectable hepatocellular carcinoma (ORIENTAL): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study. Lancet Gastroenterol Hepatol. 2018 Jan;3(1):37-46. Epub 2017 Oct 4. [https://doi.org/10.1016/S2468-1253(17)30290-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/28988687 PubMed] NCT01465464
 
−
=Adjuvant therapy=
 
−
==TACE monotherapy {{#subobject:50f9da|Regimen=1}}==
 
−
TACE: '''<u>T</u>'''rans-'''<u>A</u>'''rterial '''<u>C</u>'''hemo-'''<u>E</u>'''mbolization
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, doxorubicin-based {{#subobject:f55d49|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://clincancerres.aacrjournals.org/content/24/9/2074 Wang et al. 2018 (LCI-125-009)]
 
−
|2011-2014
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Hepatocellular_carcinoma_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>OS36: 85.2% vs 77.4%<br>(HR 0.59, 95% CI 0.36-0.97)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*Curative [[Surgery#Hepatobiliary_cancer_surgery|surgical resection]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[TACE]] consisting of:
 
−
**[[Doxorubicin (Adriamycin)]] 20 to 30 mg/m<sup>2</sup>
 
−
**Lipiodol 3 to 5 mL
 
−
'''One or more treatments'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, carboplatin, epirubicin, mitomycin-based {{#subobject:f66e49|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235393/ Wei et al. 2018 (SYSUCC-HCC-ADTACE)]
 
−
|2009-2012
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Hepatocellular_carcinoma_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#1a9850" |Superior DFS<br>Median DFS: 17.45 vs 9.27 mo<br>(HR 0.70, 95% CI 0.52-0.95)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*Curative [[Surgery#Hepatobiliary_cancer_surgery|surgical resection]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[TACE]] consisting of:
 
−
**[[Carboplatin (Paraplatin)]] 200 mg/m<sup>2</sup>
 
−
**[[Mitomycin (Mutamycin)]] 6 mg/m<sup>2</sup>
 
−
**[[Epirubicin (Ellence)]] 40 mg/m<sup>2</sup>
 
−
**Lipiodol 4 to 5 mL
 
−
'''One or two treatments'''
 
−
</div></div>
 
−
===References===
 
−
#'''LCI-125-009:''' Wang Z, Ren Z, Chen Y, Hu J, Yang G, Yu L, Yang X, Huang A, Zhang X, Zhou S, Sun H, Wang Y, Ge N, Xu X, Tang Z, Lau W, Fan J, Wang J, Zhou J. Adjuvant transarterial chemoembolization for HBV-related hepatocellular carcinoma after resection: a randomized controlled study. Clin Cancer Res. 2018 May 1;24(9):2074-2081. Epub 2018 Feb 2. [http://clincancerres.aacrjournals.org/content/24/9/2074 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29420221 PubMed] NCT01966133
 
−
#'''SYSUCC-HCC-ADTACE:''' Wei W, Jian PE, Li SH, Guo ZX, Zhang YF, Ling YH, Lin XJ, Xu L, Shi M, Zheng L, Chen MS, Guo RP. Adjuvant transcatheter arterial chemoembolization after curative resection for hepatocellular carcinoma patients with solitary tumor and microvascular invasion: a randomized clinical trial of efficacy and safety. Cancer Commun (Lond). 2018 Oct 10;38(1):61. [https://cancercommun.biomedcentral.com/articles/10.1186/s40880-018-0331-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235393/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30305149 PubMed] NCT02788526
 
−
=First-line therapy for advanced or metastatic disease=
 
−
''Note: in this setting, first-line refers to first-line systemic therapy; many patients had resection, ablation, and/or TACE prior to systemic therapy. See individual trials for details.''
 
−
==Atezolizumab & Bevacizumab {{#subobject:7d73tc|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:59biab|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa1915745 Finn et al. 2020 (IMbrave150)]
 
−
|2018-2019
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Sorafenib_monotherapy|Sorafenib]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 19.2 vs 13.4 mo<br>(HR 0.66, 95% CI 0.52-0.85)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2021 update.''<br>
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Eligibility criteria====
 
−
*Excluded: Child-Pugh class B and C, coinfection with hepatitis B or C virus, and untreated or incompletely treated esophageal or gastric varices
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Atezolizumab (Tecentriq)]] 1200 mg IV once on day 1, '''given first'''
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1, '''given second'''
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''IMbrave150:''' Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. [https://doi.org/10.1056/nejmoa1915745 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32402160 PubMed] NCT03434379
 
−
##'''Update:''' Cheng AL, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Lim HY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Ma N, Nicholas A, Wang Y, Li L, Zhu AX, Finn RS. Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs sorafenib for unresectable hepatocellular carcinoma. J Hepatol. 2022 Apr;76(4):862-873. Epub 2021 Dec 11. [https://doi.org/10.1016/j.jhep.2021.11.030 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34902530/ PubMed]
 
−
==Bevacizumab monotherapy {{#subobject:7dbb4c|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:51c13b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635806/ Siegel et al. 2008]
 
−
|2003-2006
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#88419d; color:white " |ORR: 13% (95% CI, 3-23)
 
−
|-
 
−
|}
 
−
''Note: The dose here was a pre-planned escalation dose with initial dose of 5mg/kg. The study met and exceeded primary endpoint of determining whether bevacizumab improved 6 month PFS from 40-60% (observed 6 months PFS was 65%).''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1
 
−
'''14-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Siegel AB, Cohen EI, Ocean A, Lehrer D, Goldenberg A, Knox JJ, Chen H, Clark-Garvey S, Weinberg A, Mandeli J, Christos P, Mazumdar M, Popa E, Brown RS Jr, Rafii S, Schwartz JD. Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma. J Clin Oncol. 2008 Jun 20;26(18):2992-8. [https://doi.org/10.1200/jco.2007.15.9947 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635806/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18565886 PubMed]
 
−
==Capecitabine & Bevacizumab {{#subobject:b24110|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f3fd07|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844032/ Hsu et al. 2010]
 
−
|2005-2006
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#6e016b; color:white " |ORR: 9%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 800 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 7.5 mg/kg IV once on day 1
 
−
'''21-day cycle for 6 or more cycles depending on response'''
 
−
</div></div>
 
−
===References===
 
−
#Hsu CH, Yang TS, Hsu C, Toh HC, Epstein RJ, Hsiao LT, Chen PJ, Lin ZZ, Chao TY, Cheng AL. Efficacy and tolerability of bevacizumab plus capecitabine as first-line therapy in patients with advanced hepatocellular carcinoma. Br J Cancer. 2010 Mar 16;102(6):981-6. Epub 2010 Feb 16. [https://doi.org/10.1038/sj.bjc.6605580 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844032/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20160718 PubMed]
 
−
==CapeOx {{#subobject:a86027|Regimen=1}}==
 
−
CapeOX: '''<u>Cape</u>'''citabine, '''<u>OX</u>'''aliplatin
 
−
<br>XELOX: '''<u>XEL</u>'''oda (Capecitabine), '''<u>OX</u>'''aliplatin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:912834|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360397/ Boige et al. 2007 (FFCD 03-03)]
 
−
|2003-2004
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#bfd3e6" |DCR: 72% (95% CI, 57-83)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''FFCD 03-03:''' Boige V, Raoul JL, Pignon JP, Bouché O, Blanc JF, Dahan L, Jouve JL, Dupouy N, Ducreux M; Fédération Francophone de Cancérologie Digestive. Multicentre phase II trial of capecitabine plus oxaliplatin (XELOX) in patients with advanced hepatocellular carcinoma: FFCD 03-03 trial. Br J Cancer. 2007 Oct 8;97(7):862-7. Epub 2007 Sep 18. [https://doi.org/10.1038/sj.bjc.6603956 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360397/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/17876335 PubMed]
 
−
==CapeOx & Bevacizumab {{#subobject:32787f|Regimen=1}}==
 
−
CapeOX & Bevacizumab: '''<u>Cape</u>'''citabine, '''<u>OX</u>'''aliplatin, Bevacizumab
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:231bcb|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/cncr.25889 Sun et al. 2011]
 
−
|2004-2007
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#e0ecf4" |DCR: 77.5%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 5 mg/kg IV once on day 1
 
−
**Infusion times are 75 to 105 minutes for the first dose, which if tolerated could be decreased to 50 to 70 minutes for the second dose, then 20 to 40 minutes for dose 3 and later
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Sun W, Sohal D, Haller DG, Mykulowycz K, Rosen M, Soulen MC, Caparro M, Teitelbaum UR, Giantonio B, O'Dwyer PJ, Shaked A, Reddy R, Olthoff K. Phase 2 trial of bevacizumab, capecitabine, and oxaliplatin in treatment of advanced hepatocellular carcinoma. Cancer. 2011 Jul 15;117(14):3187-92. Epub 2011 Jan 24. [https://doi.org/10.1002/cncr.25889 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21264839 PubMed]
 
−
==Doxorubicin monotherapy {{#subobject:2e9077|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 50 mg/m<sup>2</sup> {{#subobject:50ecb0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2012.44.5643 Qin et al. 2013 (EACH)]
 
−
|2007-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FOLFOX4|FOLFOX4]]
 
−
| style="background-color:#fee08b" |Trend towards inferior OS
 
−
|-
 
−
|}
 
−
''Note: EACH included patients with both Child-Pugh stage A and B disease (AST or ALT less than 2.5x ULN, T bil less than 1.5x ULN, INR less than 1.5).''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 60 mg/m<sup>2</sup> x 6 {{#subobject:16d763|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://academic.oup.com/jnci/article/97/20/1532/2521445 Yeo et al. 2005]
 
−
|1999-2003
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#PIAF_99|PIAF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycle for up to 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 60 mg/m<sup>2</sup> x 9 {{#subobject:16h213|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140673678907353 Johnson et al. 1978]
 
−
|1976-1977
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://jamanetwork.com/journals/jama/fullarticle/186918 Abou-Alfa et al. 2010 (Study 11546)]
 
−
|2005-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Doxorubicin_.26_Sorafenib_88|Doxorubicin & Sorafenib]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycle for up to 9 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 60 mg/m<sup>2</sup>, indefinite {{#subobject:1a8b63|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19880801)62:3%3C479::AID-CNCR2820620306%3E3.0.CO;2-L Lai et al. 1988]
 
−
|NR
 
−
| style="background-color:#1a9851" |Randomized (E-esc)
 
−
|[[Hepatocellular_carcinoma_-_null_regimens#Best_supportive_care|Best supportive care]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.08.4046 Gish et al. 2007 (ZARIX-ZX101-301)]
 
−
|2000-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Nolatrexed_monotherapy_77|Nolatrexed]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|}
 
−
''Note: this was the lower bound of the dosing range provided by Lai et al. 1988.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
**ZARIX-ZX101-301: Initial dose reduction to 30 mg/m<sup>2</sup> IV for patients with T bili <u>greater than</u> 1.2 mg/dL
 
−
'''21-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, 75 mg/m<sup>2</sup> {{#subobject:1a9963|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://academic.oup.com/jnci/article/97/20/1532/2521445 Yeo et al. 2005]
 
−
|1999-2003
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#PIAF_99|PIAF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycle 1: 60 mg/m<sup>2</sup> IV once on day 1
 
−
**Cycle 2 onwards, if "well tolerated": 75 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Johnson PJ, Williams R, Thomas H, Sherlock S, Murray-Lyon IM. Induction of remission in hepatocellular carcinoma with doxorubicin. Lancet. 1978 May 13;1(8072):1006-9. [https://doi.org/10.1016/S0140673678907353 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/76932 PubMed]
 
−
#Lai CL, Wu PC, Chan GC, Lok AS, Lin HJ. Doxorubicin versus no antitumor therapy in inoperable hepatocellular carcinoma: a prospective randomized trial. Cancer. 1988 Aug 1;62(3):479-83. [https://doi.org/10.1002/1097-0142(19880801)62:3%3C479::AID-CNCR2820620306%3E3.0.CO;2-L link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2839280 PubMed]
 
−
#Yeo W, Mok TS, Zee B, Leung TW, Lai PB, Lau WY, Koh J, Mo FK, Yu SC, Chan AT, Hui P, Ma B, Lam KC, Ho WM, Wong HT, Tang A, Johnson PJ. A randomized phase III study of doxorubicin versus cisplatin/interferon alpha-2b/doxorubicin/fluorouracil (PIAF) combination chemotherapy for unresectable hepatocellular carcinoma. J Natl Cancer Inst. 2005 Oct 19;97(20):1532-8. [https://academic.oup.com/jnci/article/97/20/1532/2521445 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16234567 PubMed]
 
−
#'''ZARIX-ZX101-301:''' Gish RG, Porta C, Lazar L, Ruff P, Feld R, Croitoru A, Feun L, Jeziorski K, Leighton J, Gallo J, Kennealey GT. Phase III randomized controlled trial comparing the survival of patients with unresectable hepatocellular carcinoma treated with nolatrexed or doxorubicin. J Clin Oncol. 2007 Jul 20;25(21):3069-75. [https://doi.org/10.1200/jco.2006.08.4046 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17634485 PubMed] NCT00012324
 
−
#'''Study 11546:''' Abou-Alfa GK, Johnson P, Knox JJ, Capanu M, Davidenko I, Lacava J, Leung T, Gansukh B, Saltz LB. Doxorubicin plus sorafenib vs doxorubicin alone in patients with advanced hepatocellular carcinoma: a randomized trial. JAMA. 2010 Nov 17;304(19):2154-60. [https://jamanetwork.com/journals/jama/fullarticle/186918 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21081728 PubMed] NCT00108953
 
−
#'''EACH:''' Qin S, Bai Y, Lim HY, Thongprasert S, Chao Y, Fan J, Yang TS, Bhudhisawasdi V, Kang WK, Zhou Y, Lee JH, Sun Y. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol. 2013 Oct 1;31(28):3501-8. Epub 2013 Aug 26. [https://doi.org/10.1200/JCO.2012.44.5643 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23980077 PubMed] NCT00471965
 
−
==Erlotinib & Bevacizumab {{#subobject:9afef8|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:112b09|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2008.18.3301 Thomas et al. 2009]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#9ebcda" |PFS<sub>16</sub>: 62.5%
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896238/ Philip et al. 2011]
 
−
|2006-2008
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#6e016b; color:white " |ORR: 5% (95% CI, 0-23)
 
−
|-
 
−
|}
 
−
''Note: Patients in Thomas et al. 2009 could have up to one prior systemic treatment.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Erlotinib (Tarceva)]] 150 mg PO once per day
 
−
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Thomas MB, Morris JS, Chadha R, Iwasaki M, Kaur H, Lin E, Kaseb A, Glover K, Davila M, Abbruzzese J. Phase II trial of the combination of bevacizumab and erlotinib in patients who have advanced hepatocellular carcinoma. J Clin Oncol. 2009 Feb 20;27(6):843-50. Epub 2009 Jan 12. [https://doi.org/10.1200/jco.2008.18.3301 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19139433 PubMed]
 
−
#Philip PA, Mahoney MR, Holen KD, Northfelt DW, Pitot HC, Picus J, Flynn PJ, Erlichman C. Phase 2 study of bevacizumab plus erlotinib in patients with advanced hepatocellular cancer. Cancer. 2012 May 1;118(9):2424-30. Epub 2011 Sep 27. [https://doi.org/10.1002/cncr.26556 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896238/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21953248 PubMed]
 
−
==FULV {{#subobject:7bb459|Regimen=1}}==
 
−
FULV: 5-'''<u>FU</u>''' & '''<u>L</u>'''euco'''<u>V</u>'''orin (Folinic acid)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:d1e198|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[http://www.karger.com/Article/Abstract/227516 Porta et al. 1995]
 
−
|NR in abstract
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#8c6bb1" |ORR: 28% (95% CI, 10-46)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 370 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Porta C, Moroni M, Nastasi G, Arcangeli G. 5-Fluorouracil and d,l-leucovorin calcium are active to treat unresectable hepatocellular carcinoma patients: preliminary results of a phase II study. Oncology. 1995 Nov-Dec;52(6):487-91. [http://www.karger.com/Article/Abstract/227516 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7478436 PubMed]
 
−
==FOLFOX4 {{#subobject:deff6c|Regimen=1}}==
 
−
FOLFOX4: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:3cca17|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2012.44.5643 Qin et al. 2013 (EACH)]
 
−
|2007-2009
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Doxorubicin_monotherapy|Doxorubicin]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS<br>Median OS: 6.4 vs 5.0 mo<br>(HR 0.80, 95% CI 0.63-1.02)
 
−
|-
 
−
|}
 
−
''Note: This study included patients with both Child-Pugh stage A and B disease (AST or ALT less than 2.5x ULN, T bil less than 1.5x ULN, INR less than 1.5).''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 & 2, '''given second''', then 600 mg/m<sup>2</sup> IV continuous infusion over 22 hours after each bolus (total dose per cycle: 2000 mg/m<sup>2</sup>)
 
−
*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 & 2, '''given first'''
 
−
*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
 
−
'''14-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''EACH:''' Qin S, Bai Y, Lim HY, Thongprasert S, Chao Y, Fan J, Yang TS, Bhudhisawasdi V, Kang WK, Zhou Y, Lee JH, Sun Y. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol. 2013 Oct 1;31(28):3501-8. Epub 2013 Aug 26. [https://doi.org/10.1200/JCO.2012.44.5643 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23980077 PubMed] NCT00471965
 
−
#'''SHR-1210-III-305-HCC:''' NCT03605706
 
−
==mFOLFOX & Sorafenib {{#subobject:7dbb4c|Regimen=1}}==
 
−
mFOLFOX & Sorafenib: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin, Sorafenib
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:51c13b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320284/ Goyal et al. 2019 (MGH 12-218)]
 
−
|2013-2017
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#88419d; color:white " |mTTP: 7.7 mo (95% CI, 4.4-8.9)
 
−
|-
 
−
|}
 
−
''Note: Patients had improved mTTP, but increased incidence of hepatotoxicity. Note that the regimen specifies that 5-FU be given at 1200 mg/m<sup>2</sup>/day over 46 hours; the total dose is therefore unclear.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Eligibility criteria====
 
−
*Child Pugh A with advanced HCC with no prior systemic therapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)|Fluorouracil]] 1200 mg/m<sup>2</sup>/day IV continuous infusion over 46 hours, started on day 1
 
−
*[[Folinic acid (Leucovorin)|Leucovorin]] 200 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Oxaliplatin (Eloxatin)|Oxaliplatin]] 85 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Sorafenib (Nexavar)|Sorafenib]] 400 mg twice per day
 
−
'''14-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''MGH 12-218:''' Goyal L, Zheng H, Abrams TA, Miksad R, Bullock AJ, Allen JN, Yurgelun MB, Clark JW, Kambadakone A, Muzikansky A, Knowles M, Galway A, Afflitto AJ, Dinicola CF, Regan E, Hato T, Mamessier E, Shigeta K, Jain RK, Duda DG, Zhu AX. A Phase II and Biomarker Study of Sorafenib Combined with Modified FOLFOX in Patients with Advanced Hepatocellular Carcinoma. Clin Cancer Res. 2019 Jan 1;25(1):80-89. Epub 2018 Sep 6. [https://clincancerres.aacrjournals.org/content/25/1/80 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320284/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30190369 PubMed] NCT01775501
 
−
==FOFLFOX-HAIC {{#subobject:jiuga2|Variant=1}}==
 
−
FOLFOX-HAIC: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin '''<u>H</u>'''epatic '''<u>A</u>'''rterial '''<u>I</u>'''nfusion '''<u>C</u>'''hemotherapy
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1v568 |Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.21.00608 Li et al. 2021 (HCC-S023)]
 
−
|2016-2018
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|[[#TACE_monotherapy|TACE]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 23.1 vs 16.1 mo<br>(HR 0.58, 95% CI 0.45-0.75)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IA over 60 minutes once on day 1, '''given second'''
 
−
*[[Fluorouracil (5-FU)|Fluorouracil]] 400 mg/m<sup>2</sup> IA bolus once on day 1, '''given third''', then 2400 mg/m<sup>2</sup> IA continuous infusion over 24 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
 
−
*[[Oxaliplatin (Eloxatin)|Oxaliplatin]] 130 mg/m<sup>2</sup> IA over 2 hours once on day 1, '''given first'''
 
−
'''21-day cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''HCC-S023:''' Li QJ, He MK, Chen HW, Fang WQ, Zhou YM, Xu L, Wei W, Zhang YJ, Guo Y, Guo RP, Chen MS, Shi M. Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin Versus Transarterial Chemoembolization for Large Hepatocellular Carcinoma: A Randomized Phase III Trial. J Clin Oncol. 2022 Jan 10;40(2):150-160. Epub 2021 Oct 14. [https://doi.org/10.1200/jco.21.00608 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34648352/ PubMed] NCT02973685
 
−
==FOFLFOX-HAIC & Sorafenib {{#subobject:jix4b2|Variant=1}}==
 
−
FOLFOX-HAIC & Sorafenib: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin '''<u>H</u>'''epatic '''<u>A</u>'''rterial '''<u>I</u>'''nfusion '''<u>C</u>'''hemotherapy & Sorafenib
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:0eb568 |Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512278/ He et al. 2019 (HCC-S021)]
 
−
|2016-2017
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Sorafenib_monotherapy|Sorafenib]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 13.4 vs 7.1 mo<br>(HR 0.35, 95% CI 0.26-0.48)
 
−
|-
 
−
|}
 
−
''Note: All patient who were hepatitis B received preemptive antiviral therapy.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Eligibility criteria====
 
−
*HCC with portal vein invasion confirmed by 2 imaging techniques, Child-Pugh A class liver function, and an ECOG PS of 0 to 2
 
−
*Excluded: Patients with esophageal or gastric variceal bleeding and hepatic encephalopathy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IA once on day 1
 
−
*[[Fluorouracil (5-FU)|Fluorouracil]] 400 mg/m<sup>2</sup> IA bolus once on day 1, then 2400 mg/m<sup>2</sup> IA continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
 
−
*[[Oxaliplatin (Eloxatin)|Oxaliplatin]] 85 mg/m<sup>2</sup> IA once on day 1
 
−
====Targeted therapy====
 
−
*[[Sorafenib (Nexavar)|Sorafenib]] 400 mg twice per day
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''HCC-S021:''' He M, Li Q, Zou R, Shen J, Fang W, Tan G, Zhou Y, Wu X, Xu L, Wei W, Le Y, Zhou Z, Zhao M, Guo Y, Guo R, Chen M, Shi M. Sorafenib Plus Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin vs Sorafenib Alone for Hepatocellular Carcinoma With Portal Vein Invasion: A Randomized Clinical Trial. JAMA Oncol. 2019 Jul 1;5(7):953-960. [https://doi.org/10.1001/jamaoncol.2019.0250 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512278/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31070690 PubMed] NCT02774187
 
−
==GemOx {{#subobject:b3749a|Regimen=1}}==
 
−
GemOx: '''<u>Gem</u>'''citabine, '''<u>Ox</u>'''aliplatin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a6a6da|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/cncr.22532 Louafi et al. 2007]
 
−
|2002-2004
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#88419d; color:white " |ORR: 18% (95% CI, 8–34)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Oxaliplatin (Eloxatin)]] 100 mg/m<sup>2</sup> IV over 2 hours once on day 2
 
−
'''14-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Louafi S, Boige V, Ducreux M, Bonyhay L, Mansourbakht T, de Baere T, Asnacios A, Hannoun L, Poynard T, Taïeb J. Gemcitabine plus oxaliplatin (GEMOX) in patients with advanced hepatocellular carcinoma (HCC): results of a phase II study. Cancer. 2007 Apr 1;109(7):1384-90. [https://doi.org/10.1002/cncr.22532 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17330837 PubMed]
 
−
#'''Retrospective:''' Zaanan A, Williet N, Hebbar M, Dabakuyo TS, Fartoux L, Mansourbakht T, Dubreuil O, Rosmorduc O, Cattan S, Bonnetain F, Boige V, Taïeb J. Gemcitabine plus oxaliplatin in advanced hepatocellular carcinoma: A large multicenter AGEO study. J Hepatol. 2013 Jan;58(1):81-8. Epub 2012 Sep 16. [http://www.journal-of-hepatology.eu/article/S0168-8278(12)00695-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22989572 PubMed]
 
−
==GemOx & Sorafenib {{#subobject:32787f|Regimen=1}}==
 
−
GemOx & Sorafenib: '''<u>Gem</u>'''citabine, '''<u>Ox</u>'''aliplatin , '''<u>Sorafenib</u>'''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:231bcb|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734663/ Assenat et al. 2019 (PRODIGE 10)]
 
−
|2008-2011
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|[[#Sorafenib_monotherapy|Sorafenib]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS4
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)|Gemcitabine]] 1000 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Oxaliplatin (Eloxatin)|Oxaliplatin]] 100 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Sorafenib (Nexavar)|Sorafenib]] 400 mg twice per day
 
−
'''14-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''PRODIGE 10:''' Assenat E, Pageaux GP, Thézenas S, Peron JM, Bécouarn Y, Seitz JF, Merle P, Blanc JF, Bouché O, Ramdani M, Poujol S, de Forges H, Ychou M, Boige V. Sorafenib alone vs sorafenib plus GEMOX as 1st-line treatment for advanced HCC: the phase II randomised PRODIGE 10 trial. Br J Cancer. 2019 Apr;120(9):896-902. Epub 2019 Apr 4. [https://doi.org/10.1038/s41416-019-0443-4 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734663/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30944458 PubMed] NCT00941967
 
−
==Lenvatinib monotherapy {{#subobject:c13df9|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:3a12b5|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(18)30207-1 Kudo et al. 2018 (REFLECT)]
 
−
|2013-2015
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#Sorafenib_monotherapy|Sorafenib]]
 
−
| style="background-color:#eeee01" |Non-inferior OS<br>Median OS: 13 vs 12.3 mo<br>(HR 0.92, 95% CI 0.79-1.06)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenvatinib (Lenvima)]] by the following weight-based criteria:
 
−
**Less than 60 kg: 8 mg PO once per day
 
−
**60 kg or more: 12 mg PO once per day
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''REFLECT:''' Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173. Epub 2018 Feb 9. [https://doi.org/10.1016/S0140-6736(18)30207-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29433850 PubMed] NCT01761266
 
−
#'''CheckMate 9DW:''' NCT04039607
 
−
#'''LEAP-002:''' NCT03713593
 
−
==Sorafenib monotherapy {{#subobject:b38f69|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f3a095|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.01.3441 Abou-Alfa et al. 2006b]
 
−
|2002-2003
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa0708857 Llovet et al. 2008 (SHARP)]
 
−
|2005-2006
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[Hepatocellular_carcinoma_-_null_regimens#Placebo_2|Placebo]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 10.7 vs 7.9 mo<br>(HR 0.69, 95% CI 0.55-0.87)
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045%2808%2970285-7 Cheng et al. 2008 (Sorafenib AP)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Hepatocellular_carcinoma_-_null_regimens#Placebo_2|Placebo]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 6.5 vs 4.2 mo<br>(HR 0.68, 95% CI 0.50-0.93)
 
−
|-
 
−
|[http://theoncologist.alphamedpress.org/content/14/1/70.long Pinter et al. 2009]
 
−
|2006-2007
 
−
| style="background-color:#ffffbe" |Retrospective
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2012.45.8372 Cheng et al. 2013 (SUN 1170)]
 
−
|2008-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Hepatocellular_carcinoma_-_historical#Sunitinib_monotherapy|Sunitinib]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 10.2 vs 7.9 mo<br>(HR 0.77, 95% CI 0.67-0.88)
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2012.48.4410 Johnson et al. 2013 (BRISK-FL)]
 
−
|2009-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Brivanib_monotherapy_77|Brivanib]]
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279237/ Cainap et al. 2014 (LIGHT)]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Linifanib_monotherapy_77|Linifanib]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2013.53.7746 Zhu et al. 2014 (SEARCH)]
 
−
|2009-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Erlotinib_.26_Sorafenib_99|Erlotinib & Sorafenib]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdw054 Koeberle et al. 2016 (SAKK 77/08; SASL 29)]
 
−
|2009-2013
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#Everolimus_.26_Sorafenib_99|Everolimus & Sorafenib]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS3
 
−
|-
 
−
|[http://link.springer.com/article/10.1007/s12032-013-0655-z Abdel-Rahman et al. 2013]
 
−
|2010-2011
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[Hepatocellular_carcinoma_-_historical#Capecitabine_monotherapy|Capecitabine]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 7.1 vs 5.1 mo<br>(HR 0.42, 95% CI 0.21-0.85)
 
−
|-
 
−
|[https://doi.org/10.1016/s2468-1253(18)30078-5 Kudo et al. 2018 (SILIUS)]
 
−
|2010-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#HAI_Cisplatin_.26_Fluorouracil_.28CF.29_.26_Sorafenib_99|HAI CF & Sorafenib]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735405/ Abou-Alfa et al. 2019 (CALGB 80802)]
 
−
|2010-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Doxorubicin_.26_Sorafenib_99|Doxorubicin & Sorafenib]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.76.0892 Chow et al. 2018 (SIRveNIB)]
 
−
|2010-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Radioembolization|SIRT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1016/j.jhep.2019.04.021 Jouve et al. 2019 (PRODIGE-11)]
 
−
|2010-NR in abstract
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Pravastatin_.26_Sorafenib_99|Pravastatin & Sorafenib]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(17)30683-6 Vilgrain et al. 2017 (SARAH)]
 
−
|2011-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Radioembolization|SIRT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://www.journal-of-hepatology.eu/article/S0168-8278(18)32580-7 Park et al. 2018 (STAH)]
 
−
|2013-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#TACE_.26_Sorafenib_99|Sorafenib & TACE]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(18)30207-1 Kudo et al. 2018 (REFLECT)]
 
−
|2013-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Lenvatinib_monotherapy|Lenvatinib]]
 
−
| style="background-color:#eeee01" |Non-inferior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512278/ He et al. 2019 (HCC-S021)]
 
−
|2016-2017
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#HAIC_.26_Sorafenib|SoraHAIC]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(21)00604-5 Yau et al. 2021 (CheckMate 459)]
 
−
|2016-2017
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Hepatocellular_carcinoma_-_historical#Nivolumab_monotherapy|Nivolumab]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445562/ Qin et al. 2021]
 
−
|2016-2018
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Donafenib_monotherapy_77|Donafenib]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.21.01963 Lyu et al. 2021 (FOHAIC-1)]
 
−
|2017-2020
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#HAI_FOLFOX_88|HAI FOLFOX]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa1915745 Finn et al. 2020 (IMbrave150)]
 
−
|2018-2019
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Atezolizumab_.26_Bevacizumab|Atezolizumab & Bevacizumab]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1016/s1470-2045(22)00326-6 Kelley et al. 2022 (COSMIC-312)]
 
−
| rowspan="2" |2018-2020
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Cabozantinib_.26_Atezolizumab_88|Cabozantinib & Atezolizumab]]
 
−
| style="background-color:#d73027" |Inferior PFS<sup>1</sup>
 
−
|-
 
−
|2. [[#Cabozantinib_monotherapy_88|Cabozantinib]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(21)00252-7 Ren et al. 2021 (ORIENT-32)]
 
−
|2019-2020
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#IBI305_.26_Sintilimab_77|IBI305 & Sintilimab]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>The co-primary endpoint of OS was not met at the interim analysis.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Sorafenib (Nexavar)]] 400 mg PO twice per day
 
−
**Dose/schedule changes due to toxicity include 400 mg PO once per day, 400 mg PO every other day, 200 mg PO twice per day, 200 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
#Abou-Alfa GK, Schwartz L, Ricci S, Amadori D, Santoro A, Figer A, De Greve J, Douillard JY, Lathia C, Schwartz B, Taylor I, Moscovici M, Saltz LB. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol. 2006 Sep 10;24(26):4293-300. Epub 2006 Aug 14. [https://doi.org/10.1200/jco.2005.01.3441 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16908937 PubMed]
 
−
#'''SHARP:''' Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, Cosme de Oliveira A, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378-90. [https://doi.org/10.1056/NEJMoa0708857 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18650514 PubMed] NCT00105443
 
−
##'''Subgroup analysis:''' Bruix J, Raoul JL, Sherman M, Mazzaferro V, Bolondi L, Craxi A, Galle PR, Santoro A, Beaugrand M, Sangiovanni A, Porta C, Gerken G, Marrero JA, Nadel A, Shan M, Moscovici M, Voliotis D, Llovet JM. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial. J Hepatol. 2012 Oct;57(4):821-9. Epub 2012 Jun 19. [https://www.journal-of-hepatology.eu/article/S0168-8278(12)00440-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22727733 PubMed]
 
−
#'''Sorafenib AP:''' Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009 Jan;10(1):25-34. Epub 2008 Dec 16. [https://doi.org/10.1016/S1470-2045%2808%2970285-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19095497 PubMed] NCT00492752
 
−
##'''Subgroup analysis:''' Cheng AL, Guan Z, Chen Z, Tsao CJ, Qin S, Kim JS, Yang TS, Tak WY, Pan H, Yu S, Xu J, Fang F, Zou J, Lentini G, Voliotis D, Kang YK. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to baseline status: Subset analyses of the phase III Sorafenib Asia-Pacific trial. Eur J Cancer. 2012 Jul;48(10):1452-65. Epub 2012 Jan 10. [https://www.ejcancer.com/article/S0959-8049(11)01031-8 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22240282 PubMed]
 
−
#'''Retrospective:''' Pinter M, Sieghart W, Graziadei I, Vogel W, Maieron A, Königsberg R, Weissmann A, Kornek G, Plank C, Peck-Radosavljevic M. Sorafenib in unresectable hepatocellular carcinoma from mild to advanced stage liver cirrhosis. Oncologist. 2009 Jan;14(1):70-6. Epub 2009 Jan 14. [http://theoncologist.alphamedpress.org/content/14/1/70.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/19144684 PubMed]
 
−
#Abdel-Rahman O, Abdel-Wahab M, Shaker M, Abdel-Wahab S, Elbassiony M, Ellithy M. Sorafenib versus capecitabine in the management of advanced hepatocellular carcinoma. Med Oncol. 2013 Sep;30(3):655. Epub 2013 Jul 4. [http://link.springer.com/article/10.1007/s12032-013-0655-z link to original article] [https://pubmed.ncbi.nlm.nih.gov/23824645 PubMed]
 
−
#'''BRISK-FL:''' Johnson PJ, Qin S, Park JW, Poon RT, Raoul JL, Philip PA, Hsu CH, Hu TH, Heo J, Xu J, Lu L, Chao Y, Boucher E, Han KH, Paik SW, Robles-Aviña J, Kudo M, Yan L, Sobhonslidsuk A, Komov D, Decaens T, Tak WY, Jeng LB, Liu D, Ezzeddine R, Walters I, Cheng AL. Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: results from the randomized phase III BRISK-FL study. J Clin Oncol. 2013 Oct 1;31(28):3517-24. Epub 2013 Aug 26. [https://doi.org/10.1200/JCO.2012.48.4410 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23980084 PubMed] NCT00858871
 
−
<!-- Presented at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011. -->
 
−
#'''SUN 1170:''' Cheng AL, Kang YK, Lin DY, Park JW, Kudo M, Qin S, Chung HC, Song X, Xu J, Poggi G, Omata M, Pitman Lowenthal S, Lanzalone S, Yang L, Lechuga MJ, Raymond E. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial. J Clin Oncol. 2013 Nov 10;31(32):4067-75. Epub 2013 Sep 30. [https://doi.org/10.1200/jco.2012.45.8372 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24081937 PubMed] NCT00699374
 
−
#'''LIGHT:''' Cainap C, Qin S, Huang WT, Chung IJ, Pan H, Cheng Y, Kudo M, Kang YK, Chen PJ, Toh HC, Gorbunova V, Eskens FA, Qian J, McKee MD, Ricker JL, Carlson DM, El-Nowiem S. Linifanib versus Sorafenib in patients with advanced hepatocellular carcinoma: results of a randomized phase III trial. J Clin Oncol. 2015 Jan 10;33(2):172-9. Epub 2014 Dec 8. [https://doi.org/10.1200/JCO.2013.54.3298 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279237/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25488963 PubMed] NCT01009593
 
−
#'''SEARCH:''' Zhu AX, Rosmorduc O, Evans TR, Ross PJ, Santoro A, Carrilho FJ, Bruix J, Qin S, Thuluvath PJ, Llovet JM, Leberre MA, Jensen M, Meinhardt G, Kang YK. SEARCH: a phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma. J Clin Oncol. 2015 Feb 20;33(6):559-66. Epub 2014 Dec 29. [https://doi.org/10.1200/JCO.2013.53.7746 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25547503 PubMed] NCT0901901
 
−
#'''SAKK 77/08; SASL 29:''' Koeberle D, Dufour JF, Demeter G, Li Q, Ribi K, Samaras P, Saletti P, Roth AD, Horber D, Buehlmann M, Wagner AD, Montemurro M, Lakatos G, Feilchenfeldt J, Peck-Radosavljevic M, Rauch D, Tschanz B, Bodoky G; Swiss Group for Clinical Cancer Research; SASL. Sorafenib with or without everolimus in patients with advanced hepatocellular carcinoma (HCC): a randomized multicenter, multinational phase II trial (SAKK 77/08 and SASL 29). Ann Oncol. 2016 May;27(5):856-61. Epub 2016 Feb 15. [https://doi.org/10.1093/annonc/mdw054 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26884590 PubMed] NCT01005199
 
−
#'''SARAH:''' Vilgrain V, Pereira H, Assenat E, Guiu B, Ilonca AD, Pageaux GP, Sibert A, Bouattour M, Lebtahi R, Allaham W, Barraud H, Laurent V, Mathias E, Bronowicki JP, Tasu JP, Perdrisot R, Silvain C, Gerolami R, Mundler O, Seitz JF, Vidal V, Aubé C, Oberti F, Couturier O, Brenot-Rossi I, Raoul JL, Sarran A, Costentin C, Itti E, Luciani A, Adam R, Lewin M, Samuel D, Ronot M, Dinut A, Castera L, Chatellier G; SARAH Trial Group. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1624-1636. Epub 2017 Oct 26. [https://doi.org/10.1016/S1470-2045(17)30683-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29107679 PubMed] NCT01482442
 
−
#'''REFLECT:''' Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173. Epub 2018 Feb 9. [https://doi.org/10.1016/S0140-6736(18)30207-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29433850 PubMed] NCT01761266
 
−
#'''SIRveNIB:''' Chow PKH, Gandhi M, Tan SB, Khin MW, Khasbazar A, Ong J, Choo SP, Cheow PC, Chotipanich C, Lim K, Lesmana LA, Manuaba TW, Yoong BK, Raj A, Law CS, Cua IHY, Lobo RR, Teh CSC, Kim YH, Jong YW, Han HS, Bae SH, Yoon HK, Lee RC, Hung CF, Peng CY, Liang PC, Bartlett A, Kok KYY, Thng CH, Low AS, Goh ASW, Tay KH, Lo RHG, Goh BKP, Ng DCE, Lekurwale G, Liew WM, Gebski V, Mak KSW, Soo KC; Asia-Pacific Hepatocellular Carcinoma Trials Group. SIRveNIB: selective internal radiation therapy versus sorafenib in Asia-Pacific patients with hepatocellular carcinoma. J Clin Oncol. 2018 Jul 1;36(19):1913-1921. Epub 2018 Mar 2. [https://doi.org/10.1200/JCO.2017.76.0892 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29498924 PubMed] NCT01135056
 
−
#'''SILIUS:''' Kudo M, Ueshima K, Yokosuka O, Ogasawara S, Obi S, Izumi N, Aikata H, Nagano H, Hatano E, Sasaki Y, Hino K, Kumada T, Yamamoto K, Imai Y, Iwadou S, Ogawa C, Okusaka T, Kanai F, Akazawa K, Yoshimura KI, Johnson P, Arai Y; SILIUS study group. Sorafenib plus low-dose cisplatin and fluorouracil hepatic arterial infusion chemotherapy versus sorafenib alone in patients with advanced hepatocellular carcinoma (SILIUS): a randomised, open label, phase 3 trial. Lancet Gastroenterol Hepatol. 2018 Jun;3(6):424-432. Epub 2018 Apr 7. [https://doi.org/10.1016/s2468-1253(18)30078-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29631810 PubMed] NCT01214343
 
−
#'''STAH:''' Park JW, Kim YJ, Kim DY, Bae SH, Paik SW, Lee YJ, Kim HY, Lee HC, Han SY, Cheong JY, Kwon OS, Yeon JE, Kim BH, Hwang J. Sorafenib with or without concurrent transarterial chemoembolization in patients with advanced hepatocellular carcinoma: the phase III STAH trial. J Hepatol. 2019 Apr;70(4):684-691. Epub 2018 Dec 6. [https://www.journal-of-hepatology.eu/article/S0168-8278(18)32580-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30529387 PubMed] NCT01829035
 
−
#'''PRODIGE-11:''' Jouve JL, Lecomte T, Bouché O, Barbier E, Khemissa Akouz F, Riachi G, Nguyen Khac E, Ollivier-Hourmand I, Debette-Gratien M, Faroux R, Villing AL, Vergniol J, Ramee JF, Bronowicki JP, Seitz JF, Legoux JL, Denis J, Manfredi S, Phelip JM; FFCD. Pravastatin combination with sorafenib does not improve survival in advanced hepatocellular carcinoma. J Hepatol. 2019 Sep;71(3):516-522. Epub 2019 May 22. [https://doi.org/10.1016/j.jhep.2019.04.021 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31125576 PubMed] NCT01075555
 
−
#'''HCC-S021:''' He M, Li Q, Zou R, Shen J, Fang W, Tan G, Zhou Y, Wu X, Xu L, Wei W, Le Y, Zhou Z, Zhao M, Guo Y, Guo R, Chen M, Shi M. Sorafenib Plus Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin vs Sorafenib Alone for Hepatocellular Carcinoma With Portal Vein Invasion: A Randomized Clinical Trial. JAMA Oncol. 2019 Jul 1;5(7):953-960. [https://doi.org/10.1001/jamaoncol.2019.0250 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512278/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31070690 PubMed] NCT02774187
 
−
#'''CALGB 80802:''' Abou-Alfa GK, Shi Q, Knox JJ, Kaubisch A, Niedzwiecki D, Posey J, Tan BR Jr, Kavan P, Goel R, Lammers PE, Bekaii-Saab TS, Tam VC, Rajdev L, Kelley RK, El Dika I, Zemla T, Potaracke RI, Balletti J, El-Khoueiry AB, Harding JH, Suga JM, Schwartz LH, Goldberg RM, Bertagnolli MM, Meyerhardt J, O'Reilly EM, Venook AP. Assessment of Treatment With Sorafenib Plus Doxorubicin vs Sorafenib Alone in Patients With Advanced Hepatocellular Carcinoma: Phase 3 CALGB 80802 Randomized Clinical Trial. JAMA Oncol. 2019 Nov 1;5(11):1582-1588. Epub 2019 Sep 5. [https://jamanetwork.com/journals/jamaoncology/article-abstract/2749258 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735405/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31486832 PubMed] NCT01015833
 
−
#'''IMbrave150:''' Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. [https://doi.org/10.1056/nejmoa1915745 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32402160 PubMed] NCT03434379
 
−
##'''Update:''' Cheng AL, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Lim HY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Ma N, Nicholas A, Wang Y, Li L, Zhu AX, Finn RS. Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs sorafenib for unresectable hepatocellular carcinoma. J Hepatol. 2022 Apr;76(4):862-873. Epub 2021 Dec 11. [https://doi.org/10.1016/j.jhep.2021.11.030 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34902530/ PubMed]
 
−
#'''ORIENT-32:''' Ren Z, Xu J, Bai Y, Xu A, Cang S, Du C, Li Q, Lu Y, Chen Y, Guo Y, Chen Z, Liu B, Jia W, Wu J, Wang J, Shao G, Zhang B, Shan Y, Meng Z, Wu J, Gu S, Yang W, Liu C, Shi X, Gao Z, Yin T, Cui J, Huang M, Xing B, Mao Y, Teng G, Qin Y, Wang J, Xia F, Yin G, Yang Y, Chen M, Wang Y, Zhou H, Fan J; ORIENT-32 study group. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study. Lancet Oncol. 2021 Jul;22(7):977-990. Epub 2021 Jun 15. [https://doi.org/10.1016/s1470-2045(21)00252-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34143971/ PubMed] NCT03794440
 
−
#Qin S, Bi F, Gu S, Bai Y, Chen Z, Wang Z, Ying J, Lu Y, Meng Z, Pan H, Yang P, Zhang H, Chen X, Xu A, Cui C, Zhu B, Wu J, Xin X, Wang J, Shan J, Chen J, Zheng Z, Xu L, Wen X, You Z, Ren Z, Liu X, Qiu M, Wu L, Chen F. Donafenib Versus Sorafenib in First-Line Treatment of Unresectable or Metastatic Hepatocellular Carcinoma: A Randomized, Open-Label, Parallel-Controlled Phase II-III Trial. J Clin Oncol. 2021 Sep 20;39(27):3002-3011. Epub 2021 Jun 29. [https://doi.org/10.1200/jco.21.00163 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445562/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34185551 PubMed]
 
−
#'''CheckMate 459:''' Yau T, Park JW, Finn RS, Cheng AL, Mathurin P, Edeline J, Kudo M, Harding JJ, Merle P, Rosmorduc O, Wyrwicz L, Schott E, Choo SP, Kelley RK, Sieghart W, Assenat E, Zaucha R, Furuse J, Abou-Alfa GK, El-Khoueiry AB, Melero I, Begic D, Chen G, Neely J, Wisniewski T, Tschaika M, Sangro B. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2022 Jan;23(1):77-90. Epub 2021 Dec 13. [https://doi.org/10.1016/s1470-2045(21)00604-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34914889/ PubMed] NCT02576509
 
−
#'''FOHAIC-1:''' Lyu N, Wang X, Li JB, Lai JF, Chen QF, Li SL, Deng HJ, He M, Mu LW, Zhao M. Arterial Chemotherapy of Oxaliplatin Plus Fluorouracil Versus Sorafenib in Advanced Hepatocellular Carcinoma: A Biomolecular Exploratory, Randomized, Phase III Trial (FOHAIC-1). J Clin Oncol. 2022 Feb 10;40(5):468-480. Epub 2021 Dec 14. [https://doi.org/10.1200/jco.21.01963 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34905388/ PubMed] NCT03164382
 
−
#'''COSMIC-312:''' Kelley RK, Rimassa L, Cheng AL, Kaseb A, Qin S, Zhu AX, Chan SL, Melkadze T, Sukeepaisarnjaroen W, Breder V, Verset G, Gane E, Borbath I, Rangel JDG, Ryoo BY, Makharadze T, Merle P, Benzaghou F, Banerjee K, Hazra S, Fawcett J, Yau T. Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Aug;23(8):995-1008. Epub 2022 Jul 4. [https://doi.org/10.1016/s1470-2045(22)00326-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/35798016/ PubMed] NCT03755791
 
−
#'''CheckMate 9DW:''' NCT04039607
 
−
#'''HIMALAYA:''' NCT03298451
 
−
#'''RATIONALE 301:''' NCT03412773
 
−
#'''SHR-1210-III-310:''' NCT03764293
 
−
==TACE, then 5-FU {{#subobject:572d2d|Regimen=1}}==
 
−
TACE, then 5-FU: '''<u>T</u>'''rans-'''<u>A</u>'''rterial '''<u>C</u>'''hemo'''<u>E</u>'''mbolization followed by '''<u>5</u>'''-'''<u>F</u>'''luoro'''<u>U</u>'''racil
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:b440c9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363838/ Kawata et al. 2001]
 
−
|1990-1993
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|TACE, then 5-FU & Pravastatin
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, TACE portion====
 
−
*[[Doxorubicin (Adriamycin)]] 30 mg IA once on day 1, '''given first'''
 
−
*Gelatin-sponge particles and ethyl ester of poppyseed oil fatty acids containing 38% iodine by weight (Lipiodol; AndreGelbe Laboratories, Paris, France)
 
−
'''One treatment, followed in 2 weeks by:'''
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 200 mg PO once per day
 
−
'''2-month course'''
 
−
</div></div>
 
−
===References===
 
−
#Kawata S, Yamasaki E, Nagase T, Inui Y, Ito N, Matsuda Y, Inada M, Tamura S, Noda S, Imai Y, Matsuzawa Y. Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma: a randomized controlled trial. Br J Cancer. 2001 Apr 6;84(7):886-91. [https://www.nature.com/articles/6691716 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363838/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/11286466 PubMed]
 
−
=Subsequent lines of therapy=
 
−
==Apatinib monotherapy {{#subobject:ao594c|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:913ap2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s2468-1253(21)00109-6 Qin et al. 2021 (AHELP)]
 
−
|2014-2017
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Hepatocellular_carcinoma_-_null_regimens#Placebo|Placebo]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 8.7 vs 6.8 mo<br>(HR 0.79, 95% CI 0.62-0.998)
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Apatinib (Aitan)]] 750 mg once per day
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''AHELP:''' Qin S, Li Q, Gu S, Chen X, Lin L, Wang Z, Xu A, Chen X, Zhou C, Ren Z, Yang L, Xu L, Bai Y, Chen L, Li J, Pan H, Cao B, Fang W, Wu W, Wang G, Cheng Y, Yu Z, Zhu X, Jiang D, Lu Y, Wang H, Xu J, Bai L, Liu Y, Lin H, Wu C, Zhang Y, Yan P, Jin C, Zou J. Apatinib as second-line or later therapy in patients with advanced hepatocellular carcinoma (AHELP): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2021 May 7:S2468-1253(21)00109-6. Epub ahead of print. [https://doi.org/10.1016/s2468-1253(21)00109-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33971141/ PubMed] NCT02329860
 
−
==Cabozantinib monotherapy {{#subobject:a20f66 |Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:0eb568 |Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1717002 Abou-Alfa et al. 2018 (CELESTIAL)]
 
−
|2013-2017
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[Hepatocellular_carcinoma_-_null_regimens#Placebo_3|Placebo]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 10.2 vs 8 mo<br>(HR 0.76, 95% CI 0.63-0.92)
 
−
|-
 
−
|}
 
−
''Note: Retrospective analysis demonstrated cabozantinib was safe and effective in patients with patients with Child Pugh class A and patients who progressed to Child Pugh class B.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Cabozantinib (Cometriq)]] 60 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
#'''CELESTIAL:''' Abou-Alfa GK, Meyer T, Cheng AL, El-Khoueiry AB, Rimassa L, Ryoo BY, Cicin I, Merle P, Chen Y, Park JW, Blanc JF, Bolondi L, Klümpen HJ, Chan SL, Zagonel V, Pressiani T, Ryu MH, Venook AP, Hessel C, Borgman-Hagey AE, Schwab G, Kelley RK. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med. 2018 Jul 5;379(1):54-63. [https://doi.org/10.1056/NEJMoa1717002 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29972759 PubMed] NCT01908426
 
−
#'''Retrospective:''' El-Khoueiry A, Meyer T, Cheng A, Rimassa L, Sen S,  Milwee S ,  Kelley R,  Abou-Alfa G. Outcomes for patients with advanced hepatocellular carcinoma and Child-Pugh B liver function in the phase 3 CELESTIAL study of cabozantinib vs placebo. Annals of Oncology. 2020 Jul 1-4;31(3):S220. [https://www.sciencedirect.com/science/article/pii/S0923753420393236 link to original article]
 
−
==Camrelizumab monotherapy {{#subobject:c701c3|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:d1dde0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(20)30011-5 Qin et al. 2020 (SHR-1210-II/III-HCC)]
 
−
|2016-2017
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Camrelizumab (AiRuiKa)]] 3 mg/kg IV once on day 1
 
−
'''14- to 21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''SHR-1210-II/III-HCC:''' Qin S, Ren Z, Meng Z, Chen Z, Chai X, Xiong J, Bai Y, Yang L, Zhu H, Fang W, Lin X, Chen X, Li E, Wang L, Chen C, Zou J. Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial. Lancet. 2020 Apr;21(4):571-580. Epub 2020 Feb 26. [https://doi.org/10.1016/S1470-2045(20)30011-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32112738/ PubMed] NCT02989922
 
−
==Doxorubicin monotherapy {{#subobject:5e66ea|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f77e8e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2012.44.5643 Qin et al. 2013 (EACH)]
 
−
|2007-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FOLFOX4_2|FOLFOX4]]
 
−
| style="background-color:#fee08b" |Trend toward inferior OS
 
−
|-
 
−
|[https://doi.org/10.1016/S2468-1253(19)30040-8 Merle et al. 2019 (RELIVE)]
 
−
|2012-2017
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|Doxorubicin-loaded nanoparticles
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: The EACH study required evidence of HBV or HCV with cirrhosis, and included patients with both Child-Pugh stage A and B disease (AST or ALT less than 2.5x ULN, T bili less than 1.5x ULN, INR less than 1.5x ULN; patients with AST and ALT less than 5x ULN were included if T bili was within normal limits). RELIVE did not specify control regimens in the abstract but stated "any systemic anticancer therapy (except sorafenib) as per investigator decision."''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''EACH:''' Qin S, Bai Y, Lim HY, Thongprasert S, Chao Y, Fan J, Yang TS, Bhudhisawasdi V, Kang WK, Zhou Y, Lee JH, Sun Y. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol. 2013 Oct 1;31(28):3501-8. Epub 2013 Aug 26. [https://doi.org/10.1200/JCO.2012.44.5643 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23980077 PubMed] NCT00471965
 
−
#'''RELIVE:''' Merle P, Blanc JF, Phelip JM, Pelletier G, Bronowicki JP, Touchefeu Y, Pageaux G, Gerolami R, Habersetzer F, Nguyen-Khac E, Casadei-Gardini A, Borbath I, Tran A, Wege H, Saad AS, Colombo M, Abergel A, Richou C, Waked I, Yee NS, Molé A, Attali P, Le Boulicaut J, Vasseur B; RELIVE Investigators. Doxorubicin-loaded nanoparticles for patients with advanced hepatocellular carcinoma after sorafenib treatment failure (RELIVE): a phase 3 randomised controlled trial. Lancet Gastroenterol Hepatol. 2019 Jun;4(6):454-465. Epub 2019 Apr 4. [https://doi.org/10.1016/S2468-1253(19)30040-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30954567 PubMed] NCT01655693
 
−
==FOLFOX4 {{#subobject:dd7aac|Regimen=1}}==
 
−
FOLFOX4: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:bf1b55|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2012.44.5643 Qin et al. 2013 (EACH)]
 
−
|2007-2009
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Doxorubicin_monotherapy_2|Doxorubicin]]
 
−
| style="background-color:#d9ef8b" |Trend towards superior OS
 
−
|}
 
−
''Note: The EACH study required evidence of HBV or HCV with cirrhosis, and included patients with both Child-Pugh stage A and B disease (AST or ALT < 2.5x ULN, T bil < than 1.5x ULN, INR < 1.5 ULN; patients with AST and ALT < 5x ULN were included if T bili was within normal limits).''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 & 2, '''given second''', then 600 mg/m<sup>2</sup> IV continuous infusion over 22 hours after each bolus (total dose per cycle: 2000 mg/m<sup>2</sup>)
 
−
*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 & 2, '''given first'''
 
−
*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
 
−
'''14-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''EACH:''' Qin S, Bai Y, Lim HY, Thongprasert S, Chao Y, Fan J, Yang TS, Bhudhisawasdi V, Kang WK, Zhou Y, Lee JH, Sun Y. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol. 2013 Oct 1;31(28):3501-8. Epub 2013 Aug 26. [https://doi.org/10.1200/JCO.2012.44.5643 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23980077 PubMed] NCT00471965
 
−
==Ipilimumab & Nivolumab {{#subobject:7391fe|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1c2329|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7530824/ Yau et al. 2020 (CheckMate 040)]
 
−
|2012-2016
 
−
| style="background-color:#91cf61" |Phase 1/2 (RT)
 
−
|-
 
−
|}
 
−
''Note: this is Arm A of this trial, which compared three variants of ipi/nivo dosing.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Ipilimumab (Yervoy)]] as follows:
 
−
**Cycles 1 to 4: 3 mg/kg IV once on day 1
 
−
*[[Nivolumab (Opdivo)]] as follows:
 
−
**Cycles 1 to 4: 1 mg/kg IV once on day 1
 
−
**Cycle 5 onwards: 240 mg IV once on day 1
 
−
'''21-day cycle for 4 cycles, then 14-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- #'''Abstract:''' Yau T, Kang YK, Kim TY, El-Khoueiry AB, Santoro A, Sangro B, Melero I, Kudo M, Hou MM, Matilla A, Tovoli F, Knox JJ, He AR, El-Rayes BF, Acosta-Rivera M, Neely J, Shen Y, Baccan C, Dela Cruz CM, Hsu C. Nivolumab (NIVO) + ipilimumab (IPI) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Results from CheckMate 040. Journal of Clinical Oncology. 2019 May 26; 37(15)suppl.4012 [https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.4012 link to original article] NCT01658878 -->
 
−
#'''CheckMate 040:''' Yau T, Kang YK, Kim TY, El-Khoueiry AB, Santoro A, Sangro B, Melero I, Kudo M, Hou MM, Matilla A, Tovoli F, Knox JJ, Ruth He A, El-Rayes BF, Acosta-Rivera M, Lim HY, Neely J, Shen Y, Wisniewski T, Anderson J, Hsu C. Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients With Advanced Hepatocellular Carcinoma Previously Treated With Sorafenib: The CheckMate 040 Randomized Clinical Trial. JAMA Oncol. 2020 Nov 1;6(11):e204564. Epub 2020 Oct 1. [https://doi.org/10.1001/jamaoncol.2020.4564 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7530824/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33001135/ PubMed] NCT01658878
 
−
==Lenvatinib monotherapy {{#subobject:blen19|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a9obns|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|Awaiting publication (IMbrave251)
 
−
|2021-ongoing
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Atezolizumab_.26_Lenvatinib_66|Atezolizumab & Lenvatinib]]<br>2. [[#Atezolizumab_.26_Sorafenib_66|Atezolizumab & Sorafenib]]
 
−
| style="background-color:#d3d3d3" |TBD
 
−
|-
 
−
|}
 
−
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*Exposure to [[#Atezolizumab_.26_Bevacizumab|Atezolizumab & Bevacizumab]], with progression
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenvatinib (Lenvima)]] by the following weight-based criteria:
 
−
**Less than 60 kg: 8 mg PO once per day
 
−
**60 kg or more: 12 mg PO once per day
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''IMbrave251:''' '''contains dosing details on CT.gov''' NCT04770896
 
−
==Nivolumab monotherapy {{#subobject:7391fe|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 3 mg/kg {{#subobject:1c2329|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] '''(dose-expansion phase)'''
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(17)31046-2 El-Khoueiry et al. 2017 (CheckMate 040)]
 
−
|2012-2016
 
−
| style="background-color:#91cf61" |Phase 1/2 (RT)
 
−
| style="background-color:#88419d; color:white " |ORR: 20% (95% CI, 15–26)
 
−
|-
 
−
|}
 
−
''Note: This is the dose used in the expansion cohort of this study; patients were required to have ECOG PS 1 or less, and Child-Pugh scores of 6 or less (Child-Pugh A) for the dose expansion; Child-Pugh B7 patients were eligible for the dose-escalation phase. Patients with HBV infection were required to be receiving effective antiviral therapy (viral load < 100 IU/mL). 68% of patients in the dose expansion phase received prior sorafenib therapy.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Nivolumab (Opdivo)]] 3 mg/kg IV once on day 1
 
−
'''14-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 240 mg {{#subobject:cc97e9|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
''Note: This is the FDA-recommended dose; we are not aware of a published trial using this dose in this context.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Nivolumab (Opdivo)]] 240 mg IV once on day 1
 
−
'''14-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 480 mg {{#subobject:2e37a4|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
''Note: This is the FDA-recommended dose; we are not aware of a published trial using this dose in this context.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Nivolumab (Opdivo)]] 480 mg IV once on day 1
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''CheckMate 040:''' El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, Choo SP, Trojan J, Welling TH 3rd, Meyer T, Kang YK, Yeo W, Chopra A, Anderson J, Dela Cruz C, Lang L, Neely J, Tang H, Dastani HB, Melero I. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017 Jun 24;389(10088):2492-2502. Epub 2017 Apr 20. [https://doi.org/10.1016/S0140-6736(17)31046-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28434648 PubMed] NCT01658878
 
−
==Pembrolizumab monotherapy {{#subobject:a15f9f|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, q3wk {{#subobject:0adfd3|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(18)30351-6 Zhu et al. 2018 (KEYNOTE-224)]
 
−
|2016-2017
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
|
 
−
|ORR: 17% (95% CI, 11–26)
 
−
|-
 
−
|[https://doi.org/10.1200/jco.19.01307 Finn et al. 2020 (KEYNOTE-240)]
 
−
|2016-2017
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Hepatocellular_carcinoma_-_null_regimens#Placebo_3|Placebo]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 13.9 vs 10.6 mo<br>(HR 0.78, 95% CI 0.61-0.998)
 
−
|-
 
−
|}
 
−
''Note: All patients were Child-Pugh class A. 21.5-25.9% had hepatitis B infection and 15.5-15.6% of patients had hepatitic C infection.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
 
−
'''21-day cycle for up to 35 cycles (2 years)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, q6wk {{#subobject:0adfd3|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Pembrolizumab (Keytruda)]] 400 mg IV once on day 1
 
−
'''6-week cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''Abstract:''' Lala  M, Li  M, Sinha  V, de Alwis  D, Chartash  E, Jain  L.  A six-weekly (Q6W) dosing schedule for pembrolizumab based on an exposure-response (E-R) evaluation using modeling and simulation. J Clin Oncol. 2018;36(15, supp):3062. [https://doi.org/10.1200/JCO.2018.36.15_suppl.3062 link to original article] [https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-new-dosing-regimen-pembrolizumab FDA approval]
 
−
#'''KEYNOTE-224:''' Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D, Verslype C, Zagonel V, Fartoux L, Vogel A, Sarker D, Verset G, Chan SL, Knox J, Daniele B, Webber AL, Ebbinghaus SW, Ma J, Siegel AB, Cheng AL, Kudo M; KEYNOTE-224 investigators. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 2018 Jul;19(7):940-952. Epub 2018 Jun 3. [https://doi.org/10.1016/s1470-2045(18)30351-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29875066/ PubMed] NCT02702414
 
−
##'''Update:''' Kudo M, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer DH, Verslype C, Zagonel V, Fartoux L, Vogel A, Sarker D, Verset G, Chan SL, Knox J, Daniele B, Yau T, Gurary EB, Siegel AB, Wang A, Cheng AL, Zhu AX; KEYNOTE-224 Investigators. Updated efficacy and safety of KEYNOTE-224: a phase II study of pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib. Eur J Cancer. 2022 May;167:1-12. Epub 2022 Mar 29. [https://doi.org/10.1016/j.ejca.2022.02.009 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35364421/ PubMed]
 
−
#'''KEYNOTE-240:''' Finn RS, Ryoo BY, Merle P, Kudo M, Bouattour M, Lim HY, Breder V, Edeline J, Chao Y, Ogasawara S, Yau T, Garrido M, Chan SL, Knox J, Daniele B, Ebbinghaus SW, Chen E, Siegel AB, Zhu AX, Cheng AL; KEYNOTE-240 investigators. Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial. J Clin Oncol. 2020 Jan 20;38(3):193-202. Epub 2019 Dec 2. [https://doi.org/10.1200/jco.19.01307 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31790344 PubMed] NCT02702401
 
−
==Ramucirumab monotherapy {{#subobject:bc251c|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:981bb2|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00050-9 Zhu et al. 2015 (REACH-HCC)]
 
−
|2010-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Hepatocellular_carcinoma_-_null_regimens#Placebo_3|Placebo]]
 
−
| style="background-color:#ffffbf" |Did not meet primary outcome of OS
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30937-9 Zhu et al. 2019 (REACH-2)]
 
−
|2015-2017
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[Hepatocellular_carcinoma_-_null_regimens#Placebo_3|Placebo]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 8.5 vs 7.3 mo<br>(HR 0.71, 95% CI 0.53-0.95)
 
−
|-
 
−
|}
 
−
''Note: REACH should not be confused for the trial of the same name in CLL.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Ramucirumab (Cyramza)]] 8 mg/kg IV once on day 1
 
−
'''14-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''REACH:''' Zhu AX, Park JO, Ryoo BY, Yen CJ, Poon R, Pastorelli D, Blanc JF, Chung HC, Baron AD, Pfiffer TE, Okusaka T, Kubackova K, Trojan J, Sastre J, Chau I, Chang SC, Abada PB, Yang L, Schwartz JD, Kudo M; REACH Trial Investigators. Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2015 Jul;16(7):859-70. Epub 2015 Jun 18. [https://doi.org/10.1016/S1470-2045(15)00050-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26095784 PubMed] NCT01140347
 
−
#'''REACH-2:''' Zhu AX, Kang YK, Yen CJ, Finn RS, Galle PR, Llovet JM, Assenat E, Brandi G, Pracht M, Lim HY, Rau KM, Motomura K, Ohno I, Merle P, Daniele B, Shin DB, Gerken G, Borg C, Hiriart JB, Okusaka T, Morimoto M, Hsu Y, Abada PB, Kudo M; REACH-2 study investigators. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Feb;20(2):282-296. Epub 2019 Jan 18. [https://doi.org/10.1016/S1470-2045(18)30937-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30665869 PubMed] NCT02435433
 
−
==Regorafenib monotherapy {{#subobject:3c587e|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1c2329|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(16)32453-9 Bruix et al. 2016 (RESORCE)]
 
−
|2013-2015
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[Hepatocellular_carcinoma_-_null_regimens#Placebo_3|Placebo]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 10.6 vs 7.8 mo<br>(HR 0.63, 95% CI 0.50-0.79)
 
−
|}
 
−
''Note: The RESORCE study required patients with sorafenib tolerance of at least 400 mg/day for at least 20 days of the last 28 days of treatment, and who were ECOS PG 0-1, and with Child-Pugh A status.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Regorafenib (Stivarga)]] 160 mg PO once per day on days 1 to 21
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''RESORCE:''' Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, Pracht M, Yokosuka O, Rosmorduc O, Breder V, Gerolami R, Masi G, Ross PJ, Song T, Bronowicki JP, Ollivier-Hourmand I, Kudo M, Cheng AL, Llovet JM, Finn RS, LeBerre MA, Baumhauer A, Meinhardt G, Han G; RESORCE Investigators. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Jan 7;389(10064):56-66. Epub 2016 Dec 6. Erratum in: Lancet. 2017 Jan 7;389(10064):36. [https://doi.org/10.1016/S0140-6736(16)32453-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27932229 PubMed] NCT01774344
 
−
==Sorafenib monotherapy {{#subobject:b3hy19|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f3b9os|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|Awaiting publication (IMbrave251)
 
−
|2021-ongoing
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Atezolizumab_.26_Lenvatinib_66|Atezolizumab & Lenvatinib]]<br>2. [[#Atezolizumab_.26_Sorafenib_66|Atezolizumab & Sorafenib]]
 
−
| style="background-color:#d3d3d3" |TBD
 
−
|-
 
−
|}
 
−
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*Exposure to [[#Atezolizumab_.26_Bevacizumab|Atezolizumab & Bevacizumab]], with progression
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Sorafenib (Nexavar)]] 400 mg PO twice per day
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''IMbrave251:''' '''contains dosing details on CT.gov''' NCT04770896
 
−
=Investigational agents=
 
−
*[[Refametinib (BAY 869766)]]
 
−
[[Category:Hepatocellular carcinoma regimens]]
 
−
[[Category:Disease-specific pages]]
 
−
[[Category:Hepatobiliary cancers]]
 

Latest revision as of 00:13, 18 June 2023

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