Advanced hepatocellular carcinoma: the decisions you may face
5 treatment settings, 4 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.
First line
Atezolizumab with bevacizumab (IMbrave150) after endoscopic assessment of varices, or durvalumab with a single dose of tremelimumab (HIMALAYA); nivolumab with ipilimumab (CheckMate 9DW) where approved.
A PD-L1 blocker used in lung, liver, and bladder cancer. In 2026 it became the first drug approved based on a blood test showing leftover cancer after bladder surgery.
Bevacizumab is a humanised antibody that soaks up VEGF-A, the signal tumours use to grow new blood vessels. Approved in 2004, it partners chemotherapy in colorectal, ovarian, cervical, lung, kidney and liver cancer and glioblastoma, and adds to trifluridine/tipiracil in late-line bowel cancer; hypertension, protein in the urine and bleeding are its characteristic side effects.
A PD-L1 blocker that became standard after chemoradiation for stage III lung cancer, and now in bladder, biliary, and gastric cancers.
Tremelimumab is AstraZeneca's CTLA-4 antibody, given as a single priming dose with durvalumab and chemotherapy in lung and liver cancer.
Nivolumab was the second PD-1 blocker and is often combined with ipilimumab. Long-term data show about half of advanced melanoma patients alive at 10 years on the combination.
Ipilimumab was the first checkpoint inhibitor (2011), and proved the immune system could be unleashed against cancer.
- Tests AtezolizumabFirst-line unresectable HCC: atezolizumab + bevacizumab vs sorafenib
OS 19.2 vs 13.4 months, HR 0.66.
Overall survival (updated) (months): Atezolizumab + bevacizumab 19.2 (n=336) vs Sorafenib 13.4 (n=165) · HR 0.66 · source - Tests Durvalumab, TremelimumabFirst-line unresectable HCC: STRIDE (single priming dose tremelimumab + durvalumab) vs sorafenib
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- OS HR 0.78; 5-year OS 19.6% vs 9.4%.
- Tests Nivolumab, IpilimumabFirst-line unresectable HCC: nivolumab + ipilimumab vs lenvatinib or sorafenib
OS 23.7 vs 20.6 months, HR 0.79; ORR 36% vs 13%.
Overall survival (months): Nivolumab + ipilimumab 23.7 (n=335) vs Lenvatinib or sorafenib 20.6 (n=333) · HR 0.79 · source
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Pneumonitis (immune-mediated) · Monotherapy pooled | 3% | 0.8% |
| Hepatitis (immune-mediated) · Monotherapy pooled | 1.8% | 0.7% |
| Colitis (immune-mediated) · Monotherapy pooled | 1% | 0.5% |
| Hypothyroidism (immune-mediated) · Monotherapy pooled | 4.9% | 0.2% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Pneumonitis (any cause, PACIFIC) · vs 12.8% placebo; 1.1% fatal | 18.3% | - |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis with ipilimumab (1+3 mg/kg) · Monotherapy pooled unless stated | 25% | 14.4% |
| Hepatitis with ipilimumab · Monotherapy pooled unless stated | 15% | 13.4% |
| Colitis · Monotherapy pooled unless stated | 2.9% | 1.7% |
| Hepatitis · Monotherapy pooled unless stated | 1.8% | 1.5% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis (with nivolumab 1+3) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 25% | 14.4% |
| Hepatitis (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 15% | 13.4% |
| Rash (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 28% | 4.8% |
| Adrenal insufficiency (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 8% | 2.6% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Between Atezolizumab, Bevacizumab, Durvalumab and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in IMbrave150 and HIMALAYA, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- Which side effects of Atezolizumab or Durvalumab are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- For my situation (first line), which of the standard options do you recommend and why?Why: Guideline options include: Atezolizumab with bevacizumab (IMbrave150) after endoscopic assessment of varices, or durvalumab with a single dose of tremelimumab (HIMALAYA); nivolumab with ipilimumab (CheckMate 9DW) where approved.
- Am I a candidate for Atezolizumab, Bevacizumab, Durvalumab or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of IMbrave150 and HIMALAYA apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
First line when immunotherapy is unsuitable
Lenvatinib (REFLECT) or sorafenib (SHARP), for example after liver transplantation or with active autoimmune disease.
An oral anti-angiogenic pill that matched sorafenib in liver cancer with higher response rates, and partners with pembrolizumab in kidney and endometrial cancer.
The first drug ever to extend life in advanced liver cancer (2007), now mostly a comparator arm that newer combinations are measured against.
- Tests Lenvatinib, SorafenibFirst-line unresectable HCC: lenvatinib vs sorafenib (non-inferiority)
OS 13.6 vs 12.3 months, non-inferior (HR 0.92).
- Tests SorafenibAdvanced HCC, Child-Pugh A, no prior systemic therapy: sorafenib vs placebo
OS 10.7 vs 7.9 months, HR 0.69.
- Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
- Reduce to 14 mg (thyroid) or 10 mg (RCC) in severe impairment.
- Reduce in severe renal impairment.
- Take without food (1 hour before or 2 hours after).
- Possible QT prolongation. Check ECG and electrolytes; review other QT-prolonging drugs.
- Between Lenvatinib and Sorafenib, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in REFLECT and SHARP, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- For my situation (first line when immunotherapy is unsuitable), which of the standard options do you recommend and why?Why: Guideline options include: Lenvatinib (REFLECT) or sorafenib (SHARP), for example after liver transplantation or with active autoimmune disease.
- Am I a candidate for Lenvatinib, Sorafenib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of REFLECT and SHARP apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Second line and beyond
Lenvatinib or sorafenib after immunotherapy; regorafenib (RESORCE), cabozantinib (CELESTIAL) or ramucirumab when alpha-fetoprotein is 400 or above, all proven after sorafenib.
A sorafenib successor that became the first second-line drug proven to prolong life in liver cancer (2017).
A pill that blocks both blood-vessel growth and the MET escape pathway, used in kidney, liver, thyroid and, since 2025, neuroendocrine cancers.
An antibody that blocks the VEGF receptor, approved in liver cancer only for patients with a high AFP blood level, the first biomarker-selected HCC drug.
An oral anti-angiogenic pill that matched sorafenib in liver cancer with higher response rates, and partners with pembrolizumab in kidney and endometrial cancer.
The first drug ever to extend life in advanced liver cancer (2007), now mostly a comparator arm that newer combinations are measured against.
- Tests RegorafenibHCC progressing on sorafenib: regorafenib vs placebo
OS 10.6 vs 7.8 months, HR 0.63.
- Tests CabozantinibHCC after sorafenib (up to two prior lines): cabozantinib vs placebo
OS 10.2 vs 8.0 months, HR 0.76.
- Take with a low-fat breakfast (under 30% fat).
- Not recommended in severe impairment; hepatotoxicity is a boxed warning.
- Tablets: take on an empty stomach (no food 2 hours before or 1 hour after). Avoid grapefruit.
- Reduce to 40 mg daily in moderate impairment; avoid in severe.
- Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
- Reduce to 14 mg (thyroid) or 10 mg (RCC) in severe impairment.
- Reduce in severe renal impairment.
- Take without food (1 hour before or 2 hours after).
- Possible QT prolongation. Check ECG and electrolytes; review other QT-prolonging drugs.
- Between Regorafenib, Cabozantinib, Ramucirumab and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in RESORCE and CELESTIAL, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- For my situation (second line and beyond), which of the standard options do you recommend and why?Why: Guideline options include: Lenvatinib or sorafenib after immunotherapy; regorafenib (RESORCE), cabozantinib (CELESTIAL) or ramucirumab when alpha-fetoprotein is 400 or above, all proven after sorafenib.
- Am I a candidate for Regorafenib, Cabozantinib, Ramucirumab or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of RESORCE and CELESTIAL apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Portal vein tumour thrombus
Radiotherapy or radioembolisation to the thrombus alongside systemic therapy; hepatic artery infusion chemotherapy in Asian centres.
Stereotactic body radiotherapy converges multiple beams with sub-millimetre accuracy to deliver tumour-destroying doses in one to five outpatient sessions, doing the job of surgery for inoperable early lung cancer and for metastases in liver, spine and brain. Tumour size and location limit its use, and late toxicity is a concern near the central airways.
- Ablative doses with minimal recovery
- Outpatient
Millions of tiny radioactive glass or resin beads are injected into the liver artery, lodging in the tumour and irradiating it from within.
- Outpatient, single session
- Effective in portal vein thrombosis where TACE is contraindicated
- Radiation segmentectomy can be curative for small tumours
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Size and location limits
- Late toxicity near central airways
- Radioembolisation-induced liver disease
- Failed to beat sorafenib on OS in advanced disease
- Lung shunting excludes some patients
- Between SBRT / SABR (stereotactic radiotherapy) and Radioembolisation (TARE / SIRT, yttrium-90), which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- For my situation (portal vein tumour thrombus), which of the standard options do you recommend and why?Why: Guideline options include: Radiotherapy or radioembolisation to the thrombus alongside systemic therapy; hepatic artery infusion chemotherapy in Asian centres.
Add these to your appointment list, or take the full question set for this cancer.
Liver disease during treatment
Antiviral therapy for hepatitis B, variceal management and monitoring of liver function, which decides whether further lines are possible.
This setting names no product or technology record yet; the approach above is the standard as written. Ask your team which specific treatments they mean.
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
No side-effect rates or interaction flags are recorded for these options yet. The side-effect lookup and interaction checker cover the products that have them.
- Which specific treatments are you proposing for this setting, and what are the alternatives?Why: The standard of care here is described in words rather than named products; ask for the names.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- For my situation (liver disease during treatment), which of the standard options do you recommend and why?Why: Guideline options include: Antiviral therapy for hepatitis B, variceal management and monitoring of liver function, which decides whether further lines are possible.
Add these to your appointment list, or take the full question set for this cancer.