NAVIGATING THE EVOLVING TREATMENT LANDSCAPE IN ADVANCED HCC

Advanced HCC is characterized by unresectable tumors that are not eligible for locoregional therapy due to factors such as high tumor burden, extrahepatic metastases, poor liver function, or other comorbidities.1,2 Systemic therapies are the focus of treatment for advanced HCC.

Median overall survival mOS of standard of care (SoC) treatment classes for advanced HCC over time

SoC treatment classes for advanced HCC over time

SoC Treatment Classes for Advanced HCC Over Time Chart

Figure developed from Lai CL, et al. 1998, Chan SL, 2014, Qin S, et al. 2014, Llovet JM, et al. 2008, Kudo M 2017, Rimassa L, et al. 2025, Cheng A-L, et al. 2022, Yau T, et al. 2020.3,5–7,9,13–15

Prior to 2007, conventional chemotherapy failed to show consistent survival benefits.3,4 Commonly-used chemotherapy agents have shown mOS ranging between 11 weeks and 9 months.5–7

Following the approval of the first TKI in 2007, mOS of 9–11 months was observed in clinical trials for advanced HCC,3,8,9 and TKIs remained SoC for more than a decade.10

The first-line systemic treatment landscape for advanced HCC has evolved rapidly in recent years, shifting from TKIs towards immunotherapy-based regimens, either as combination regimens or monotherapy.11,12 Immunotherapy-based regimens have increased survival outcomes in patients with advanced HCC.11,12 Since 2017, clinical trials have demonstrated mOS ranging between 16–23 months for approved IO-containing regimens.13–15

This has improved treatment and transformed survival outcomes in patients with advanced HCC.11,12 Since 2017, clinical trials have demonstrated mOS ranging between 16–23 months for approved IO-containing regimens.13–15

Figure developed from National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®) 2025, Llovet JM, et al. 2008, Lai CL, et al. 1988, Liu J, et al. 2024, Kudo M 2018, Lazzaro A and Hartshorn KL 2023, Patel TH and Yau T, et al. 2020.1,2,4-6,9-11

Clinical guidelines

There are several clinical guidelines available that provide evidence-based recommendations for the treatment and management of advanced HCC. These guidelines are developed by the organizations below.

Clinical Guidelines Icon

Review the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)16

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Clinical Guidelines Icon

Review the AASLD Guidelines2

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Clinical Guidelines Icon

Review the BCLC Guidelines1

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Clinical Guidelines Icon

Review the ASCO Guidelines17

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Multidisciplinary Approach for Treatment Decision Making in Advanced HCC Icon

Treatment decision making in advanced HCC requires a multidisciplinary approach and consideration of several factors.

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Let HORIZONS HCC be your compass in navigating the complexities and latest developments in HCC patient care.

Abbreviations:

AASLD=American Association for the Study of Liver Diseases; ASCO=American Society of Clinical Oncology; BCLC=Barcelona Clinic Liver Cancer; HCC=hepatocellular carcinoma; IO=immuno-oncology; mOS=median overall survival; NCCN=National Comprehensive Cancer Network; SoC=standard of care; TKI=tyrosine kinase inhibitor.

References:

1. Reig M, Sanduzzi-Zamparelli M, Forner A, et al. J Hepatol. 2025:S0168-8278(25)02571-1. 2. Singal AG, Llovet JM, Yarchoan M, et al. Hepatology. 2023;78(6):1922–1965; 3. Llovet JM, Ricci S, Mazzaferro V, et al. N Engl J Med. 2008;359(4):378–390; 4. Cidon EU. World J Hepatol. 2017;9(18):797–807; 5. Lai CL, Wu PC, Chan GCB, Lok ASF, Lin HJ. Cancer. 1988;62(3):479–483; 6. Chan SL. Oncologist. 2014;19(11):1115–1117; 7. Qin S, Cheng Y, Liang J, et al. Oncologist. 2014;19(11):1169–1178; 8. Liu J, Xia S, Mohammed DM, Yang X, Zhu Y, Jiang X. Discov Oncol. 2024;15(1):259; 9. Kudo M. Liver Cancer. 2018;7(2):134–147; 10. Alqahtani SA, Colombo MG. World J Gastrointest Oncol. 2021;13(12):2038–2049; 11. Zhang H, Zhang W, Jiang L, Chen Y. Biomark Res. 2022;10(1):3; 12. Lazzaro A, Hartshorn KL. Cancers (Basel). 2023;15(9):2506; 13. Rimassa L, Chan SL, Sangro B, et al. J Hepatol. 2025;83(4):899–908; 14. Yau T, Kang YK, Kim TY, et al. JAMA Oncol. 2020;6(11):e204564; 15. Cheng A-L, Qin S, Ikeda M, et al. J Hepatol. 2022;76:862–873; 16. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Hepatocellular Carcinoma V.2.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed December 11, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way; 17. Gordan JD, Kennedy EB, Abou-Alfa GK, et al. J Clin Oncol. 2024;42(15):1830–1850.

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