Key points
- Today the first treatment for most people with advanced liver cancer is an immunotherapy combination: atezolizumab with bevacizumab, or durvalumab with tremelimumab [1, 2].
- These combinations lengthened patients' lives more than the tablet sorafenib; in one study, about 1 in every 5 patients was still alive 5 years later [8, 9, 10].
- The main condition is a liver that still works well. Your doctor checks your liver health with blood tests and an examination [1, 2].
- Before bevacizumab, an endoscopy is usually needed to find and treat swollen veins in the oesophagus and stomach (varices) that may bleed [1, 2].
- If immunotherapy is not suitable or the disease progresses, targeted tablets such as lenvatinib and sorafenib, and later drugs, can still control the disease [1, 2].
- More limited tumours can often be treated with surgery, a liver transplant, destroying the tumour with heat, or treatment through the tumour's blood vessel [3, 1].
The story of treating advanced liver cancer
In liver cancer, the liver is both where the tumour grows and the organ that has to cope with the drugs: more than 8 in every 10 patients also have cirrhosis (long-term damage and scarring of the liver) [1].
Until 2008, no effective drug was known for advanced liver cancer [5]. That year, in a large study, the tablet sorafenib gave patients a few more months of life compared with patients who did not take it, and it became the standard treatment [5, 13]. Ten years later, the tablet lenvatinib worked as well as sorafenib in a large study [6]. Both tablets block several of the tumour's growth pathways, including the formation of its new blood vessels [5, 6].
The big change came with immunotherapy: drugs that take the brakes off the immune system so that it can fight cancer cells better [15]. In 2020, the combination of atezolizumab (an immunotherapy drug) and bevacizumab (a drug that blocks the growth of new blood vessels in the tumour) lengthened patients' lives more than sorafenib in a large study [7, 8, 16]. Then the combination of durvalumab and tremelimumab [9] and the combination of nivolumab and ipilimumab [11] also lengthened patients' lives more than the tablets in large studies. In the study of durvalumab and tremelimumab, the number of patients alive 5 years later was almost twice that in the sorafenib group [10].
Who can have immunotherapy?
Immunotherapy is for liver cancer that cannot be controlled with surgery or local treatments: the tumour has reached the large blood vessels of the liver or spread outside the liver, or there are so many tumours in the liver that local treatment does not help [1, 3]. Before starting, your doctor checks the following [1, 2]:
- Liver health: a score called the "Child-Pugh" score is worked out from a few blood tests and an examination [2]. The main studies included patients whose liver was in the best group, Child-Pugh A [15, 11].
- Physical fitness: you should be able to manage your daily activities yourself [1].
- Autoimmune disease and transplant: in moderate to severe autoimmune disease and after a liver transplant, immunotherapy is not recommended, because it may harm the body or the transplanted liver; these patients are offered a targeted tablet instead [1].
- Bleeding risk: checked before bevacizumab (next section).
- Hepatitis: if you have active hepatitis B, you need antiviral medicine at the same time [2].
If the liver is weaker (Child-Pugh B), there is less evidence; selected patients may be given one of the targeted tablets or a single immunotherapy drug on its own [1]. When the liver is very weak or a person's physical fitness is very low, anticancer treatment does not lengthen life, and controlling pain and symptoms and the person's comfort come first [3, 2].
Before bevacizumab: checking for varices and bleeding risk
Bevacizumab increases the risk of bleeding [16]. In cirrhosis, the pressure in the liver's main vein (the portal vein) rises, and swollen veins called "varices" may form in the oesophagus or stomach and can bleed [1, 2]. So before starting atezolizumab and bevacizumab, an endoscopy (looking at the oesophagus and stomach with a thin tube with a camera) is usually done [1, 2]. In the main study, this check was required within the 6 months before treatment, and people who had bleeding from varices during that time were not included [15].
If large varices are found, they are usually treated before treatment starts by tying them off with small rubber bands through the endoscope; sometimes the tablet carvedilol (a blood pressure medicine) is an alternative [1]. If you have had bleeding in the last 6 months, your bleeding risk is high, or bevacizumab is unsuitable for another reason (such as a lot of protein in the urine), the combination of durvalumab and tremelimumab, which contains no bevacizumab, is a more suitable option [1].
Bevacizumab also slows wound healing; if you have surgery planned, be sure to tell your doctor beforehand [16]. During treatment, your blood pressure and urine protein are checked regularly [16].
Treatment today, step by step
- 1
Staging and liver health
Your doctor assesses how far the tumour has spread (with a CT scan or MRI), your liver health, the pressure in the liver's blood vessels, an AFP blood test and your physical fitness [2]. Guidelines recommend the "Barcelona" staging system, which links each stage to the treatment that suits it [2, 4]. See: Diagnosis and staging
- 2
If the tumour is limited: local treatment
One or a few small tumours can often be treated with surgery, a liver transplant or destroying them with heat through a needle; several tumours in the liver are usually treated by blocking the tumour's blood vessel together with a chemotherapy drug given through a catheter [3, 1]. These treatments are described in Treatment by stage.
- 3
First treatment for advanced disease: an immunotherapy combination
Atezolizumab with bevacizumab: both are given into a vein on the same day, every 3 weeks [8, 15]. Durvalumab with tremelimumab: tremelimumab only once, on the first day together with durvalumab, and after that durvalumab alone every 4 weeks [17]. Guidelines regard both as preferred first treatments [1, 2]. The combination of nivolumab and ipilimumab also lengthened patients' lives in a large study [11], but two immunotherapy drugs together cause more immune side effects [1].
- 4
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If the disease progresses
Your doctor chooses another drug. After immunotherapy, one of the targeted tablets (lenvatinib or sorafenib) is usually given [1, 2]; after sorafenib, the tablets regorafenib or cabozantinib, or ramucirumab infusions if the blood AFP level is very high. All three lengthened patients' lives in large studies [12, 13, 14].
- 6
What does treatment involve?
Atezolizumab and bevacizumab
Infusions into a vein on the same day, every 3 weeks. The first infusions take longer (about an hour for atezolizumab and about an hour and a half for bevacizumab), and if they are well tolerated, later ones are shorter [15, 16]. Treatment continues as long as it works and the side effects are manageable [15].
Durvalumab and tremelimumab
Both drugs on the first day, then durvalumab alone every 4 weeks [17]. Because it contains no bevacizumab, it is also suitable for people with a high risk of bleeding [1].
Before starting and regularly during treatment, blood tests (liver, kidney and thyroid function) are done [15], and every few months your doctor checks how well the treatment is working with a CT scan or MRI [2]. The tumour does not have to shrink a lot: in one study, any shrinkage of the tumour, or the disease staying stable, was linked with longer life [10].
Side effects: what to expect
The side effects of immunotherapy are different from those of standard chemotherapy: sometimes the immune system attacks healthy organs, such as the lungs, bowel, liver, hormone glands (thyroid, adrenal, pituitary), kidneys or skin [15]. These side effects mostly happen during treatment, but they can also occur after it has ended; spotting them early is the most important thing [15].
With atezolizumab and bevacizumab, the most common side effects were high blood pressure (about 3 in every 10 people), tiredness, protein in the urine, itching, diarrhoea and loss of appetite [15]. With durvalumab and tremelimumab, skin rash, diarrhoea, tiredness, itching and muscle pain were more common, and about 1 in every 7 people developed an underactive thyroid [17]. The targeted tablets mostly cause high blood pressure, diarrhoea, loss of appetite and weight loss (lenvatinib), or redness and pain on the palms and soles (sorafenib) [6].
Most of these side effects can be controlled with medicines, a lower dose or a short break from treatment if they are reported early [15, 19]. See: Side effects of immunotherapy
- "What stage is my cancer, and is local treatment still possible?" [3]
- "How well is my liver working, and what is my Child-Pugh score?" [2, 1]
- "Do I need an endoscopy and treatment of varices before bevacizumab?" [1]
- "Which combination suits me better, and why?" [1, 2]
- "Should my hepatitis B or C be treated too?" [2]
When should I contact my doctor?
With immunotherapy (atezolizumab, durvalumab, tremelimumab, nivolumab, ipilimumab): tell your doctor straight away about a new cough, chest pain or shortness of breath; diarrhoea, blood or mucus in your stools, or severe abdominal pain; yellowing of the skin or eyes, severe nausea or vomiting, pain on the right side of the abdomen, severe lack of energy, or bruising or bleeding easily; pelvic pain, passing urine often, or unusual swelling; a widespread rash or painful sores on the skin or in the mouth [15, 17, 18]. With bevacizumab: any serious or unusual bleeding (such as coughing or spitting up blood), severe or ongoing abdominal pain, severe constipation, vomiting, or a high fever with shivering [16]. With targeted tablets: high blood pressure, chest pain or any bleeding [19, 20]. If you vomit blood or have black stools, confusion or unusual drowsiness, or severe sudden abdominal pain, call your local emergency number straight away [15, 16, 19].
Frequently asked questions
Can immunotherapy cure advanced liver cancer?
Usually the aim is long-term control of the disease. But in some patients the disease stays under control for years: in one study, about 1 in every 5 patients was alive 5 years after starting durvalumab and tremelimumab [10]. See: Is liver cancer curable?
Which is better: atezolizumab and bevacizumab, or durvalumab and tremelimumab?
Guidelines regard both as preferred first treatments [1, 2]. The choice depends on your bleeding risk, other illnesses and circumstances; if you have recently had bleeding or have high-risk varices, the combination without bevacizumab is more suitable [1].
Does standard chemotherapy help liver cancer?
In large studies, standard chemotherapy did not lengthen the lives of people with advanced liver cancer, and the European guideline does not recommend it [2]. The main drug treatments are immunotherapy and targeted tablets [1, 2]. See: What is cancer immunotherapy?
Can I have immunotherapy if I have cirrhosis?
Can I have immunotherapy if I have hepatitis B?
Yes; in the main study of atezolizumab and bevacizumab, almost half of the patients had hepatitis B [15]. You need to take antiviral medicine throughout treatment; the European guideline recommends it for all patients with active hepatitis B, especially during cancer treatment [2].
How long does treatment last?
For physicians
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Staging and assessment: BCLC 2022: stage 0, a single tumour of 2 cm or less without vascular invasion or extrahepatic spread, with preserved liver function and no symptoms; A, a single tumour of any size or up to 3 nodules, none larger than 3 cm, without macrovascular invasion, extrahepatic spread or symptoms (PS 0); B, multifocal HCC beyond the A criteria with preserved liver function, PS 0 and no vascular invasion or extrahepatic spread (three subgroups by tumour burden and liver function); C, vascular invasion or extrahepatic spread with PS 2 or less and preserved liver function (assess for systemic therapy); D, major cancer-related symptoms (PS greater than 2) and/or impaired liver function without the option of transplantation, in whom treating the HCC does not change survival [3]. The 2026 update still links each stage directly to its evidence-based first-line treatment and adds the CUSE decision-making framework [4]. ESMO: assess liver function with Child-Pugh and/or ALBI [III, A]; BCLC for prognosis and treatment allocation [IV, A] [2]. Calculator: Child-Pugh and ALBI calculator.
First line: SHARP (602 patients): sorafenib 400 mg twice daily versus placebo, median OS 10.7 vs 7.9 months (HR 0.69) [5]. REFLECT (954 patients): lenvatinib (12 mg for body weight 60 kg or more, 8 mg for less than 60 kg) non-inferior to sorafenib, median OS 13.6 vs 12.3 months (HR 0.92; 95% CI 0.79 to 1.06) [6]. IMbrave150 (501 patients, 2:1 randomisation): atezolizumab + bevacizumab versus sorafenib, HR for death 0.58, 12-month OS 67.2% vs 54.6% and median PFS 6.8 vs 4.3 months (HR 0.59); grade 3–4 adverse events 56.5% vs 55.1% and grade 3–4 hypertension 15.2% [7]; in the updated analysis (median follow-up 15.6 months) median OS 19.2 vs 13.4 months (HR 0.66) [8]; objective response 28% vs 12% (RECIST version 1.1) [15]. HIMALAYA (1171 patients): STRIDE versus sorafenib, median OS 16.43 vs 13.77 months (HR 0.78; P=0.0035) and 36-month OS 30.7% vs 20.2%; durvalumab monotherapy non-inferior (HR 0.86); no significant difference in PFS; grade 3–4 adverse events 50.5% vs 52.4% [9]; objective response 20.1% vs 5.1% [17]; 48-month OS 25.2% vs 15.1% [24] and 60-month OS 19.6% vs 9.4% (HR 0.76) [10]. CheckMate 9DW (668 patients, Child-Pugh 5 or 6): nivolumab + ipilimumab versus lenvatinib or sorafenib, median OS 23.7 vs 20.6 months (HR 0.79; P=0.018) and 36-month OS 38% vs 24%; more deaths in the first 6 months (HR 1.65), followed by sustained separation of the curves (HR 0.61); treatment-related grade 3–4 adverse events 41% vs 42%, and 12 vs 3 treatment-related deaths [11]; objective response 36.1% vs 13.2%, with median duration of response 30.4 vs 12.9 months [18].
Guidelines: AASLD 2023: systemic therapy for Child-Pugh A or selected B, ECOG 0–1, and BCLC C or B unsuitable for locoregional therapy (level 1, strong); atezolizumab + bevacizumab or durvalumab + tremelimumab preferred in Child-Pugh A (level 2, strong); endoscopy before atezolizumab + bevacizumab (level 5, strong), at least one session of band ligation for large varices, with carvedilol as an alternative (level 5, weak), and an interval of about 2 weeks after band ligation considered reasonable; GI bleeding within the last 6 months or high-risk stigmata on endoscopy: adequate treatment of varices or durvalumab + tremelimumab (level 5, strong); both combinations contraindicated: sorafenib or lenvatinib (level 1, strong); selected Child-Pugh B: sorafenib, lenvatinib or single-agent anti-PD-1/PD-L1 (level 3, weak); avoid ICIs for recurrence after liver transplantation (level 4, strong) [1]. ESMO: atezolizumab + bevacizumab or durvalumab + tremelimumab [I, A]; screening for varices in portal hypertension before atezolizumab + bevacizumab [IV, A]; nivolumab + ipilimumab [I, B]; durvalumab monotherapy for patients unsuitable for combination therapy [I, A]; lenvatinib or sorafenib when ICIs are contraindicated [I, A]; systemic chemotherapy is not recommended [II, D] [2].
Second line: RESORCE (573 patients who tolerated sorafenib, Child-Pugh A): regorafenib 160 mg in weeks 1–3 of each 4-week cycle, median OS 10.6 vs 7.8 months (HR 0.63) [12]. CELESTIAL (707 patients, up to 2 prior regimens): cabozantinib 60 mg daily, median OS 10.2 vs 8.0 months (HR 0.76) and PFS 5.2 vs 1.9 months [13]. REACH-2 (292 patients with AFP 400 ng/mL or more): ramucirumab 8 mg/kg every 2 weeks, median OS 8.5 vs 7.3 months (HR 0.710) [14]. All these trials were done after sorafenib, and there are no high-quality data on second-line treatment after immunotherapy combinations [1]. AASLD: after atezolizumab + bevacizumab or durvalumab + tremelimumab, sorafenib or lenvatinib preferred (level 5, weak); after atezolizumab + bevacizumab, cabozantinib, regorafenib or ipilimumab + nivolumab may also be used (level 5, weak); after sorafenib or lenvatinib, cabozantinib or regorafenib (or ramucirumab if AFP 400 or more) (level 1, strong) [1]. ESMO: lenvatinib after ICI [IV, A] and sorafenib [IV, B]; regorafenib or cabozantinib after sorafenib [I, A]; ramucirumab if AFP 400 or more [I, B] [2].
| Regimen | Dose and schedule | Key points |
|---|---|---|
| Atezolizumab + bevacizumab (first line) | Atezolizumab 1200 mg IV followed by bevacizumab 15 mg/kg IV on the same day, every 3 weeks; the label also lists atezolizumab 840 mg every 2 weeks or 1680 mg every 4 weeks [8, 15] | Assess varices before starting; first infusion of atezolizumab over 60 minutes and of bevacizumab over 90 minutes; withhold bevacizumab for at least 28 days before elective surgery [1, 15, 16] |
| Lenvatinib (first line or after ICI) | 12 mg orally once daily for body weight 60 kg or more; 8 mg once daily for body weight below 60 kg [19] | Control blood pressure before starting and monitor after 1 week, then every 2 weeks for 2 months and monthly thereafter; hepatic encephalopathy 8% in REFLECT [19] |
| Sorafenib (first line or after ICI) | 400 mg orally twice daily without food (1 hour before or 2 hours after a meal) [20] | Hand-foot skin reaction usually in the first 6 weeks; monitor INR with concomitant warfarin [20] |
| Durvalumab + tremelimumab, STRIDE regimen (first line) | Tremelimumab 300 mg as a single dose followed by durvalumab 1500 mg on day 1 of cycle 1; then durvalumab 1500 mg every 4 weeks; body weight below 30 kg: tremelimumab 4 mg/kg and durvalumab 20 mg/kg [17] | No bevacizumab, an option for patients at risk of bleeding; tremelimumab infused over 60 minutes [17, 1] |
| Nivolumab + ipilimumab (first line) | Nivolumab 1 mg/kg and ipilimumab 3 mg/kg on the same day, every 3 weeks for up to 4 doses; then nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks for up to 2 years [18] | In CheckMate 9DW, nivolumab 480 mg every 4 weeks; more deaths in the first 6 months; immune-mediated hepatitis 15% and colitis 25% at this dose in melanoma or HCC [11, 18] |
| Regorafenib (after sorafenib) | 160 mg orally once daily for the first 21 days of each 28-day cycle, after a low-fat meal [21] | In RESORCE, only patients who had tolerated sorafenib [12] |
| Cabozantinib (after sorafenib) | 60 mg orally once daily [22] | Stop 3 weeks before surgery, including dental surgery [22] |
| Ramucirumab (after sorafenib, AFP 400 ng/mL or more) | 8 mg/kg IV every 2 weeks [23] | Premedicate with an IV histamine H1 antagonist before each infusion [23] |
Dose modifications for side effects, monitoring and further details are on each regimen's page.
Full doses, premedication and dose modifications: atezolizumab + bevacizumab · durvalumab + tremelimumab (STRIDE) · nivolumab + ipilimumab · lenvatinib · sorafenib · regorafenib · cabozantinib · ramucirumab. Immune toxicity: lesson on immunotherapy toxicity; hepatitis B: lesson on hepatitis B and anticancer treatment; dosing in liver impairment: lesson on dose adjustment in renal and hepatic impairment.
Scientific evidence
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Scientific evidence
13 itemsAtezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma
Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma
Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial
Sorafenib in advanced hepatocellular carcinoma
Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial
Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma
Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma
Five-year overall survival update from the HIMALAYA study of tremelimumab plus durvalumab in unresectable HCC
Nivolumab plus ipilimumab versus lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma (CheckMate 9DW): an open-label, randomised, phase 3 trial
AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma
Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment, and follow-up of patients with hepatocellular carcinoma
BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update
BCLC strategy for prognosis prediction and treatment recommendations: The 2026 update
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Related links
Related cancer types
References
24 referencesShow all references, 13 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
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- 4BCLC strategy for prognosis prediction and treatment recommendations: The 2026 update
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- 7Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma
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- 21STIVARGA (regorafenib) tablets, for oral use: Prescribing Information
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- 24Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma
This page is based on reputable scientific sources and was last updated on 29 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.
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