Systemic Therapy for Advanced Hepatocellula Carcinoma: ASCO Guideline

John D. Gordan, Erin B. Kennedy, Ghassan K. Abou-Alfa, Muhammad Shaalan Beg, Steven T. Brower, Terence P. Gade, Laura Goff, Shilpi Gupta, Jennifer Guy, William P. Harris, Renuka Iyer, Ishmael Jaiyesimi, Minaxi Jhawer, Asha Karippot, Ahmed O. Kaseb, R. Kate Kelley, Jennifer J. Knox, Jeremy Kortmansky, Andrea Leaf, William M. RemakRachna T. Shroff, Davendra P.S. Sohal, Tamar H. Taddei, Neeta K. Venepalli, Andrea Wilson, Andrew X. Zhu, Michal G. Rose

Research output: Contribution to journalReview articlepeer-review

353 Scopus citations


PURPOSE To develop an evidence-based clinical practice guideline to assist in clinical decision making for patients with advanced hepatocellular carcinoma (HCC). METHODS ASCO convened an Expert Panel to conduct a systematic review of published phase III randomized controlled trials (2007-2020) on systemic therapy for advanced HCC and provide recommended care options for this patient population. RESULTS Nine phase III randomized controlled trials met the inclusion criteria. RECOMMENDATIONS Atezolizumab 1 bevacizumab (atezo 1 bev) may be offered as first-line treatment of most patients with advanced HCC, Child-Pugh class A liver disease, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1, and following management of esophageal varices, when present, according to institutional guidelines. Where there are contraindications to atezolizumab and/or bevacizumab, tyrosine kinase inhibitors sorafenib or lenvatinib may be offered as first-line treatment of patients with advanced HCC, Child-Pugh class A liver disease, and ECOG PS 0-1. Following first-line treatment with atezo 1 bev, and until better data are available, second-line therapy with a tyrosine kinase inhibitor may be recommended for appropriate candidates. Following first-line therapy with sorafenib or lenvatinib, second-line therapy options for appropriate candidates include cabozantinib, regorafenib for patients who previously tolerated sorafenib, or ramucirumab (for patients with a-fetoprotein $ 400 ng/mL), or atezo 1 bev where patients did not have access to this option as first-line therapy. Pembrolizumab or nivolumab are also reasonable options for appropriate patients following sorafenib or lenvatinib. Consideration of nivolumab 1 ipilimumab as an option for second-line therapy and third-line therapy is discussed. Further guidance on choosing between therapy options is included within the guideline. Additional information is available at

Original languageEnglish (US)
Pages (from-to)4317-4345
Number of pages29
JournalJournal of Clinical Oncology
Issue number36
StatePublished - Dec 20 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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