Vol 17, No 4 (2021)
REVIEW ARTICLES
Published online: 2021-06-16
Systemic treatment of patients with advanced hepatocellular carcinoma
DOI: 10.5603/OCP.2020.0047
Oncol Clin Pract 2021;17(4):164-168.
Abstract
Hepatocellular carcinoma is the most common histologic type among primary liver neoplasms, which are the second cause of cancer-related deaths worldwide. Resection, ablation, liver transplantation or transarterial chemoembolization can be used in some patients but majority of patients receive systemic treatment provided their performance status is good and liver function is preserved. Overall, 5-year survival remains low and in Europe is 12%. Since 2008 sorafenib was the only drug with proven survival improvement in the first-line treatment. Regorafenib and cabozantinib showed efficacy in second-line treatment. Recently published the results of IMbrave150 trial showed that combination of atezolizumab with bevacizumab is much more effective than sorafenib in the first-line treatment. These results of IMbrave150 study will most probably change a daily-practice entirely.
Keywords: hepatocellular carcinomasystemic treatmentsorafenibatezolizumabbevacizumab
References
- Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. . CA Cancer J Clin. 2015; 65: 87–108.
- Njei B, Rotman Y, Ditah I, et al. Emerging trends in hepatocellular carcinoma incidence and mortality. Hepatology. 2015; 61(1): 191–199.
- Wojciechowska U, Didkowska J. Zachorowania i zgony na nowotwory złośliwe w Polsce. Krajowy Rejestr Nowotworów, Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie – Państwowy Instytut Badawczy. Dostępne na stronie http://onkologia.org.pl/raporty/ dostęp z dnia 12/11/2020.
- Lepage C, Capocaccia R, Hackl M, et al. EUROCARE-5 Working Group:. Survival in patients with primary liver cancer, gallbladder and extrahepatic biliary tract cancer and pancreatic cancer in Europe 1999-2007: Results of EUROCARE-5. Eur J Cancer. 2015; 51(15): 2169–2178.
- Pugh RN, Murray-Lyon IM, Dawson JL, et al. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973; 60(8): 646–649.
- Galle P, Forner A, Llovet J, et al. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018; 69(1): 182–236.
- Lai CL, Lok AF, Wu PC, et al. Doxorubicin versus no antitumor therapy in inoperable hepatocellular carcinoma. A prospective randomized trial. Cancer. 1988; 62(3): 479–483, doi: 10.1002/1097-0142(19880801)62:3<479::aid-cncr2820620306>3.0.co;2-l.
- Llovet JM, Ricci S, Mazzaferro V, et al. SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008; 359(4): 378–390.
- Cheng AL, Kang YK, Chen Z, et al. 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; 10(1): 25–34.
- Cheng AL, Kang YK, Lin DY, et al. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial. J Clin Oncol. 2013; 31(32): 4067–4075.
- Abou-Alfa GK, Shi Q, Knox JJ, et al. 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 [Epub ahead of print]; 5: 1582–1588.
- Kudo M, Finn R, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018; 391(10126): 1163–1173.
- Bruix J, Qin S, Merle P, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017; 389: 56–66.
- Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med. 2018; 379(1): 54–63.
- El-Khoueiry A, Sangro B, Yau T, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017; 389: 2492–2502.
- Yau T, Kang YK, Kim TY, et al. 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 [Epub ahead of print]; 6: e204564.
- Yau T, Park JW, Finn RS, et al. CheckMate 459: A randomized, multi-center phase III study of nivolumab (NIVO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC). ESMO Congress 2019; LBA38_PR.
- Zhu A, Finn R, Edeline J, et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 2018; 19(7): 940–952.
- Finn RS, Ryoo BY, Merle P, et 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; 38(3): 193–202.
- Finn RS, Qin S, Ikeda M, et al. IMbrave150 Investigators. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020; 382(20): 1894–1905.
- Galle PR, Finn RS, Qin S i wsp. Patient-reported outcomes from the phase III IMbrave150 trial of atezolizumab plus bevacizumab vs sorafenib as first-line treatment for patients with unresectable hepatocellular carcinoma. 2020 Gastrointestinal Cancers Symposium. Abstract 476.