Professor He and Professor Pinter, discuss their perspectives and experience on how to select systemic therapy options in first line and beyond for patients with advanced or unresectable HCC based on the current international HCC guidelines.

Insights from Professor He and Professor Pinter on the international HCC guidelines including NCCN, ASCO, ESMO, ILCA, AASLD and EASL which were revised in late 2020 and in 2021 to include atezolizumab+bevacizumab immunotherapy combination as the new standard of care in first line setting for patients with advanced or unresectable HCC. They discuss which guidelines they follow in their clinical practice and mainly how to select the first systemic therapy option for patients with advanced or unresectable HCC. An Infographic is also available proposing an algorithm providing the criteria to select between lenvatinib and sorafenib in 1L for patients not eligible for atezolizumab+bevacizumab and propose the treatment option sequencing for 2L and beyond after atezolizumab+bevacizumab for patients with advanced or unresectable HCC.


Aiwu Ruth He MD underwent medical training at Hunan Medical University in China. She then completed post graduate training at East Carolina University, USA. Dr He completed a Fellowship at Georgetown University School of Medicine in 2006 and is currently Assistant Professor in the Division of Hematology / Oncology.

Dr He has received awards from the National Institute of Health, the American Association for Cancer Research and Digestive Disease Week. She has been an invited reviewer on a number of international journals and holds membership of several professional societies. Dr He has been an investigator in various different research trials in the field of hepatocellular carcinoma.

Relevant publications:

Kim K, Jha R, Prins PA, Wang H, Chacha M, Hartley ML, He AR. Regorafenib in advanced hepatocellular carcinoma (HCC): considerations for treatment. Cancer Chemother Pharmacol 2017 Nov;80(5):945-954. doi: 10.1007/s00280-017-3431-5. Epub 2017 Sep 20.

Fu Y, Silverstein S, McCutcheon JN, Dyba M, Nath RG, Aggarwal M, Coia H, Bai A, Pan J, Jiang J, Kallakury B, Wang H, Zhang YW, Giaccone G, He AR, Chung FL. An endogenous DNA adduct as a prognostic biomarker for hepatocarcinogenesis and its prevention by Theaphenon E in mice. Hepatology 2018 Jan;67(1):159-170. doi: 10.1002/hep.29380. Epub 2017 Nov 13.

Shetty K, He AR. A STORM in a teacup?-the challenges of adjuvant therapy in hepatocellular carcinoma (HCC). Transl Gastroenterol Hepatol 2016 Mar 16;1:2. doi: 10.21037/tgh.2016.03.10. eCollection 2016.

Sarantopoulos J, Mita AC, He A, Wade JL, Hsueh CT, Morris JC, Lockhart AC, Quinn DI, Hwang J, Mier J, Zhang W, Wack C, Yin J, Clot PF, Rixe O. Safety and pharmacokinetics of cabazitaxel in patients with hepatic impairment: a phase I dose-escalation study. Cancer Chemother Pharmacol 2017 Feb;79(2):339-351. doi: 10.1007/s00280-016-3210-8.

Gabrielson A, Tesfaye A, Choradia N, Marshall J, Pishvaian M, Smaglo B, Dorsch-Vogel K, Wang H, He AR. Phase II study of temozolomide and veliparib combination therapy for sorafenib-refractory advanced hepatocellular carcinoma. Cancer Chemotherapy and Pharmacology 2015 Nov;76(5):1073-9. doi: 10.1007/s00280-015-2852-2. Epub 2015 Oct 8.

Gabrielson A, Wu Y, Wang H, Jiang J, Kallakury B, Gatalica Z, Reddy S, Kleiner D, Fishbein T, Johnson L, Island E, Satoskar R, Banovac F, Jha R, Kachhela J, Feng P, Zhang T, Tesfaye A, Prins P, Loffredo C, Marshall J, Weiner L, Atkins M, He AR. Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC. Cancer Immunol Res 2016 May;4(5):419-30. doi: 10.1158/2326-6066.CIR-15-0110. Epub 2016 Mar 11.

Tian X, Shivapurkar N, Wu Z, Hwang J, Pishvaian MJ, Weiner LM, Ley L, Zhou D, Zhi X, Wellstein A, Marshall JL, He AR. Circulating microRNA profile predicts disease progression in patients receiving second-line treatment of lapatinib and capecitabine for metastatic pancreatic cancer. Oncol Lett 2016 Mar;11(3):1645-1650. Epub 2016 Jan 13.

Gabrielson A, Miller A, Banovac F, Kim A, He AR, Unger K. Outcomes and Predictors of Toxicity after Selective Internal Radiation Therapy Using Yttrium-90 Resin Microspheres for Unresectable Hepatocellular Carcinoma. Front Oncol 2015 Dec 23;5:292. doi: 10.3389/fonc.2015.00292.

Gabrielson A, Tesfaye AA, Marshall JL, Pishvaian MJ, Smaglo B, Jha R, Dorsch-Vogel K, Wang H, He AR. Phase II study of temozolomide and veliparib combination therapy for sorafenib-refractory advanced hepatocellular carcinoma. Cancer Chemother Pharmacol 2015 Nov;76(5):1073-9. doi: 10.1007/s00280-015-2852-2. Epub 2015 Oct 8.

Wu Z, Gabrielson A, Hwang JJ, Pishvaian MJ, Weiner LM, Zhuang T, Ley L, Marshall JL, He AR. Phase II study of lapatinib and capecitabine in second-line treatment for metastatic pancreatic cancer. Cancer Chemother Pharmacol 2015 Dec;76(6):1309-14. doi: 10.1007/s00280-015-2855-z. Epub 2015 Oct 27.

Deeken JF, Wang H, Subramaniam D, He AR, Hwang J, Marshall JL, Urso CE, Wang Y, Ramos C, Steadman K, Pishvaian MJ. A phase 1 study of cetuximab and lapatinib in patients with advanced solid tumor malignancies. Cancer 2015 May 15;121(10):1645-53. doi: 10.1002/cncr.29224. Epub 2015 Jan 29.

Subramaniam D, He AR, Hwang J, Deeken J, Pishvaian M, Hartley ML, Marshall JL. Irreversible Multitargeted ErbB Family Inhibitors for Therapy of Lung and Breast Cancer. Curr Cancer Drug Targets 2015;14(9):775-93.

Cheng AL, Kang YK, He AR, Lim HY, Ryoo BY, Hung CH, Sheen IS, Izumi N, Austin T, Wang Q, Greenberg J, Shiratori S, Beckman RA, Kudo M; Investigators’ Study Group..Safety and efficacy of tigatuzumab plus sorafenib as first-line therapy in subjects with advanced hepatocellular carcinoma: A phase 2 randomized study. J Hepatol 2015 Oct;63(4):896-904. doi: 10.1016/j.jhep.2015.06.001.

Zhi X, Lin L, Yang S, Bhuvaneshwar K, Wang H, Gusev Y, Lee M, Kallakury B, Shivapurkar N, Cahn K, Tian X, Marshall J, Byers S, He AR. βII-spectrin (SPTBN1) suppresses progression of hepatocellular carcinoma and Wnt signaling via regulation of Wnt inhibitor Kallistatin. Hepatology 2014 Oct 12. doi: 10.1002/hep.27558.

Lin L, Yao Z, Bhuvaneshwar K, Gusev Y, Kallakury K, Yang X, Shetty K, and He AR. Transcriptional Regulation of STAT3 by SPTBN1 and SMAD3 in Hepatocellular Carcinoma Through cAMP-Response Element–Binding Proteins ATF3 and CREB2. Carcinogenesis 2014 Aug 5. pii: bgu163.

Rimassa L, Porta C, Borbath I, Daniele B, Finn R, Raoul J, Schwartz L, He AR, Trojan J, Peck-Radosavljevic M, Abbadessa G, Goldberg T, Santoro A, Bruix J. Tivantinib in MET-high hepatocellular carcinoma patients and the ongoing Phase III clinical trial. Hepatic Oncol 2014, doi:10.2217/HEP.14.3

Rana N., Ju A.W, Bazylewicz M, Kallakury B, He AR, Unger K, Lee J. Yttrium-90 radioembolization in patients with hepatocellular carcinoma who have previously received sorafenib. Front Oncol 2013 Dec 12; 3(323): 1-10.

Weinberg B, Wang H, Yang X, Wu C, Pishvaian M, He AR, Marshall J, Hwang J. Maintenance therapy with capecitabine in patients with resected pancreatic adenocarcinoma after adjuvant therapy, a retrospective cohort study. Gastrointest Cancer Res 2014 May;7(3-4):91-7.

Forero-Torres A, Infante J, Waterhouse D, Wong L, Arrowsmith V, He AR, Hart L,Trent D, Wade J, Jin X, Wang Q, Austin T, Rosen M, Beckman R, von Roemeling R, Greenberg J, Saleh M. Phase 2, multicenter, open-label study of tigatuzumab (CS-1008), a humanized monoclonal antibody targeting death receptor 5, in combination with gemcitabine in chemotherapy-naive patients with unresectable or metastatic pancreatic cancer. Cancer Med 2013 Dec;2(6):925-32. doi: 10.1002/cam4.137. Epub 2013 Oct 25.

Shivapurkar N, Mikhail S, Navarro R, Bai W, Marshall J, Hwang J, Pishvaian M, Wellstein A, He AR. Decrease in blood miR-296 predicts chemotherapy resistance and poor clinical outcome in patients receiving systemic chemotherapy for metastatic colon cancer. Int J Colorectal Dis 2013 Jun;28(6):887. doi: 10.1007/s00384-012-1560-1. Epub 2012 Aug 15.

Zhang JX, Li DQ, He AR, Motwani M, Vasiliou V, Eswaran J, Mishra L, Kumar R . Synergistic inhibition of hepatocellular carcinoma growth by cotargeting chromatin modifying enzymes and poly (ADP-ribose) polymerases. Hepatology 2012 Jun;55(6):1840-51.

Pishvaian MJ, Marshall JL, Wagner AJ, Hwang JJ, Malik S, Cotarla I, Deeken JF, He AR, Daniel H, Halim AB, Zahir H, Copigneaux C, Liu K, Beckman RA, Demetri GD. A phase 1 study of efatutazone, an oral peroxisome proliferator-activated receptor gamma agonist, administered to patients with advanced malignancies. Cancer 2012 Nov 1;118(21):5403-13. doi: 10.1002/cncr.27526. Epub 2012 May 8.

Pishvaian MJ, Slack R, Koh EY, Beumer JH, Hartley ML, Cotarla I, Deeken J, He AR, Hwang J, Malik S, Firozvi K, Liu M, Elston B, Strychor S, Egorin MJ, Marshall JL. A Phase I clinical trial of the combination of imatinib and paclitaxel in patients with advanced or metastatic solid tumors refractory to standard therapy. Cancer Chemother Pharmacol 2012 Dec;70(6):843-53. doi: 10.1007/s00280-012-1969-9. Epub 2012 Sep 27.

Kunz PL, He AR, Colevas AD, Pishvaian MJ, Hwang JJ, Clemens PL, Messina M, Kaleta R, Abrahao F, Sikic BI, Marshall JL.2012. Phase I trial of ixabepilone administered as three oral doses each separated by 6 hours every 3 weeks in patients with advanced solid tumors. Invest New Drugs 2012 Dec; 30(6): 2364-2370.

Dr Aiwu Ruth He has received financial support/sponsorship for research support, consultation, or speaker fees from the following companies:

Genentech and MERCK 

Dr Matthias Pinter works at the Medical University of Vienna in Austria where he also received both his MD and PhD. He is board-certified for Internal Medicine and Gastroenterology and Hepatology. Since 2017, he has led the hepatocellular carcinoma programme and research group at the Division of Gastroenterology and Hepatology at the Medical University of Vienna. His main research interests include the systemic treatment of liver cancer, particularly the identification of prognostic markers and scores that may help to identify patients most likely to benefit from specific therapies. To broaden his knowledge and expertise in basic research and experimental oncology, he worked as a research fellow and postdoc at renowned institutions, including the University of Bern in Switzerland and the Massachusetts General Hospital/Harvard Medical School in the United States. He has published numerous original papers and review articles on liver cancer in prestigious peer-reviewed journals covering the categories oncology, gastroenterology and hepatology, and radiology.

Assoc. Prof. Matthias Pinter has received financial support/sponsorship for research support, consultation, or speaker fees from the following companies:

Bayer, BMS, Ipsen, Eisai, Lilly, MSD and Roche.

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