For the next installment of our Guidelines Side-By-Side series, we’re going to take a look at the current guidelines for liver cancer. This article will examine how the recommendations in each guideline agree, contradict, or otherwise differ.
Our topic for today will be systemic treatment for metastatic hepatocellular carcinoma. The focus will be limited to systemic therapies. The five organizations and guidelines we will be looking at today include:
ASCO - Systemic Therapy for Advanced Hepatocellular Carcinoma (March 2024)
NCCN - Hepatocellular Carcinoma (April 2024)
AGA - Systemic Therapy for Hepatocellular Carcinoma (February 2022)
AASLD - Prevention, Diagnosis, and Treatment of Hepatocellular Carcinoma (May 2023)
SITC - Immunotherapy for the Treatment of Hepatocellular Carcinoma (September 2023)
Before jumping into the recommendations, here are a couple key differences in terms of methodology and scope to take into consideration:
| Item | ASCO | NCCN | AGA | AASLD | SITC |
| Publication Year | 2024 | 2024 | 2022 | 2023 | 2023 |
| Methodology Rigor | Most Rigorous | Somewhat Rigorous | Most Rigorous | Somewhat Rigorous | Somewhat Rigorous |
| Uses GRADE? | Yes | No | Yes | No | No |
| Primary Audience | Oncologists | Oncologists | Gastroenterologists | Gastroenterologists | Oncologists |
| Comments | Limited to systemic therapy | N/A | Limited to systemic therapy | N/A | Limited to immunotherapies |
Recommended HCC Regiments per Society:
| Treatment | ASCO | NCCN | AGA | AASLD | SITC |
| First Line | atezolizumab + bevacizumab OR durvalumab + tremelimumab OR lenvatinib OR sorafenib OR durvalumab | atezolizumab + bevacizumab OR durvalumab + tremelimumab OR lenvatinib OR sorafenib OR pembrolizumab OR durvalumab | atezolizumab + bevacizumab OR lenvatinib OR sorafenib | atezolizumab + bevacizumab OR durvalumab + tremelimumab OR lenvatinib OR sorafenib OR pembrolizumab OR nivolumab | atezolizumab + bevacizumab OR durvalumab + tremelimumab OR lenvatinib OR sorafenib OR nivolumab |
| Subsequent Lines | sorafenib OR lenvatinib OR cabozantinib OR ramucirumab OR regorafenib OR durvalumab OR pembrolizumab OR nivolumab OR atezolizumab + bevacizumab OR durvalumab + tremelimumab OR nivolumab + ipilimumab | cabozantinib OR regorafenib OR lenvatinib OR sorafenib OR nivolumab + ipilimumab OR pembrolizumab OR ramucirumab OR nivolumab OR dostarlimab-gxly OR selpercatinib | cabozantinib OR pembrolizumab OR regorafenib OR ramucirumab | sorafenib OR lenvatinib OR cabozantinib OR regorafenib PR ipilimumab plus nivolumab PR ramucirumab OR pembrolizumab | pembrolizumab OR nivolumab |
Additional Comments on Treatment Approach Per Society:
| Notes | ASCO | NCCN | AGA | AASLD | SITC |
| First Line | Preferred first line therapy is atezolizumab + bevacizumab OR durvalumab + tremelimumab | Preferred first line therapy is atezolizumab + bevacizumab OR durvalumab + tremelimumab | Preferred first line therapy is atezolizumab+bevacizumab | Preferred first line therapy is atezolizumab + bevacizumab OR durvalumab + tremelimumab | Preferred first line therapy is atezolizumab + bevacizumab OR durvalumab + tremelimumab |
| Subsequent Lines | Recommendations differ depending on the therapy chosen first line. Past second line, choose medication with mechanism of action that differs from prior therapies | Preferred second line regimens are cabozantinib OR regorafenib OR lenvatinib OR sorafenib. Also, the only guideline to include recommendations for dostarlimab-gxly OR selpercatinib | Recommendations consitent regardless of first line therapy chosen | Recommendations differ depending on the therapy chosen first line | Only PD-1 checkpoint inhibitors mentioned for second line therapy |
Specific HCC Medications Recommended Across All Five Hepatocellular Carcinoma Guidelines:
| Medications | ASCO | NCCN | AGA | AASLD | SITC |
| FIRST LINE | |||||
| atezolizumab + bevacizumab | Yes | Yes | Yes | Yes | Yes |
| durvalumab + tremelimumab | Yes | Yes | Yes | Yes | |
| nivolumab + ipilimumab | |||||
| durvalumab | Yes | Yes | |||
| tremelimumab | |||||
| atezolizumab | |||||
| bevacizumab | |||||
| sorafenib | Yes | Yes | Yes | Yes | Yes |
| lenvatinib | Yes | Yes | Yes | Yes | Yes |
| cabozantinib | |||||
| regorafenib | |||||
| ramucirumab | |||||
| pembrolizumab | Yes | Yes | |||
| nivolumab | Yes | Yes | |||
| ipilimumab | |||||
| SUBSEQUENT LINES | |||||
| atezolizumab + bevacizumab | Yes | ||||
| durvalumab + tremelimumab | Yes | ||||
| nivolumab + ipilimumab | Yes | Yes | |||
| durvalumab | Yes | ||||
| tremelimumab | |||||
| atezolizumab | |||||
| bevacizumab | |||||
| sorafenib | Yes | Yes | |||
| lenvatinib | Yes | Yes | |||
| cabozantinib | Yes | Yes | Yes | ||
| regorafenib | Yes | Yes | Yes | ||
| ramucirumab | Yes | Yes | Yes | ||
| pembrolizumab | Yes | Yes | Yes | Yes | |
| nivolumab | Yes | Yes | |||
| ipilimumab | |||||
| dostarlimab-gxly | Yes | ||||
| selpercatinib | Yes |
This concludes our Guidelines Side by Side for Systemic Therapy for Hepatocellular Carcinoma. Sign up for alerts and stay informed on the latest published guidelines and articles.
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