Key points
- Liver cancer is the third leading cause of cancer death worldwide, and about 90% of primary liver cancers are hepatocellular carcinoma (HCC) [1, 2].
- Most cases develop on a background of chronic liver disease, especially hepatitis B and C, alcohol, fatty liver disease and cirrhosis [2, 3].
- Universal hepatitis B vaccination has significantly reduced the incidence of liver cancer in children [4].
- In people with cirrhosis, an ultrasound every 6 months (together with an AFP blood test) is recommended for early detection [2, 3].
- Treatment is chosen according to the BCLC staging system [5]; in advanced disease, the immunotherapy combination atezolizumab + bevacizumab is the standard first-line treatment, and oral targeted drugs are used for patients for whom immunotherapy is not suitable and after the disease progresses [2, 7, 17, 18, 19, 22].
What is liver cancer?
The liver is the largest internal organ of the body and carries out vital tasks such as clearing toxins, making proteins and storing energy. “Primary liver cancer” is cancer that starts in the liver cells themselves; it is different from cancers that have spread to the liver from other organs (liver metastases).
The most common type of primary liver cancer is hepatocellular carcinoma, which accounts for about 90% of cases [2]. Liver cancer is the third leading cause of cancer death worldwide [1, 2]. A less common type is cholangiocarcinoma, or bile duct cancer, which is covered briefly in a separate section on this page.
Signs and symptoms
In its early stages, liver cancer usually causes no symptoms, which makes screening people at high risk all the more important [2, 3]. In more advanced stages, the following symptoms may appear:
- Pain or a feeling of fullness in the upper right part of the abdomen
- Weight loss and loss of appetite for no obvious reason
- Yellowing of the skin and eyes
- Swelling of the abdomen (ascites) or swollen legs
- Severe fatigue
- Sudden worsening in someone who previously had stable cirrhosis
Warning signs
If you develop a fever, vomit blood or pass black stools, or develop yellowing of the skin, confusion or rapid swelling of the abdomen, see a doctor or go to the emergency department immediately.
Risk factors and prevention
Most liver cancers develop in a liver that has been damaged and chronically inflamed for years. The most important risk factors are [2, 3]:
- Chronic hepatitis B infection — can lead to liver cancer even without cirrhosis.
- Chronic hepatitis C infection
- Cirrhosis of the liver from any cause
- Alcohol use
- Fatty liver disease linked to metabolic dysfunction (MASLD), which is associated with obesity and diabetes and accounts for a growing share of liver cancers.
Prevention
- Hepatitis B vaccination: after a nationwide newborn vaccination program was introduced in Taiwan, the incidence of liver cancer in children aged 6 to 14 fell from 0.70 to 0.36 per 100,000 children [4].
- Treating hepatitis B and C: effective antiviral treatment lowers the risk of liver cancer, although in people with cirrhosis the risk does not fall to zero and screening must continue [2, 3].
- Avoiding alcohol and controlling weight and diabetes to stop liver disease from progressing [2, 3].
Screening and early detection
Guidelines from the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) recommend that people at high risk, especially all patients with cirrhosis and certain groups of hepatitis B carriers without cirrhosis, have a liver ultrasound every 6 months; measuring alpha-fetoprotein (AFP) in the blood at the same time increases the sensitivity of screening [2, 3]. The aim is to find a tumor at a stage when curative treatments such as surgery, transplantation or local ablation are still possible [2, 3].
The 2025 EASL guideline emphasizes personalized screening based on individual risk assessment and the use of new tools [2].
Diagnosis and staging
Diagnostic pathway for liver cancer
- 1
Screening finding or symptoms
A lesion found on ultrasound, or a rise in AFP, in a person at high risk.
- 2
- 3
- 4
Assessing liver function
Determining liver reserve (for example with the Child-Pugh classification and ALBI) and portal venous pressure, because treatment must take into account both the tumor and the patient’s liver [5].
- 5
BCLC staging
Tumor features, liver function and the patient’s general condition are combined to determine the stage (0, A, B, C, D) and choose treatment [5].
Treatment by stage
| Stage | Features | Main treatments |
|---|---|---|
| 0 (very early) | Single tumor ≤2 cm, preserved liver function, no symptoms | Local ablation or surgery; when transplantation is not an option, external-beam radiotherapy is an alternative to ablation [5] |
| A (early) | Single tumor, or up to 3 nodules ≤3 cm, preserved liver function | Surgery, liver transplantation or ablation |
| B (intermediate) | Multiple nodules in the liver, without vascular invasion or spread outside the liver | Transplantation (in selected patients), transarterial chemoembolization (TACE) or systemic therapy [5, 22] |
| C (advanced) | Portal vein invasion or spread outside the liver, or mild cancer-related symptoms | Systemic therapy: combination immunotherapy first-line [7, 9, 11, 22]; oral targeted drugs for patients for whom immunotherapy is not suitable and after disease progression [17, 18, 19, 22, 23, 24] |
| D (end-stage) | Severe liver failure or very poor general condition | Supportive care; liver transplantation in very limited cases |
The final treatment decision is made at a multidisciplinary team meeting (hepatologist, surgeon, interventional radiologist, oncologist and radiation oncologist) [2].
Treatment options
Surgery (resection)
Liver transplantation
Treats both the tumor and the diseased liver. Under the Milan criteria (a single tumor ≤5 cm or up to 3 tumors ≤3 cm), 4-year survival of 85% was reported in patients who met the criteria [6].
Local ablation
Chemoembolization (TACE)
Radiation therapy
Drug treatment for advanced disease
Immunotherapy drugs help the body’s immune system fight cancer [8, 10, 11]. The immunotherapy combination atezolizumab + bevacizumab, given as an intravenous infusion every 3 weeks, was the first immunotherapy combination to prolong survival compared with sorafenib in a large phase 3 trial (IMbrave150) [7, 8], and it is now the standard first-line treatment [2, 22].
For patients for whom immunotherapy is not suitable, the oral drugs lenvatinib or sorafenib are recommended [2, 22]; sorafenib prolonged survival compared with placebo, and lenvatinib was not inferior to sorafenib in this respect [17, 18]. Two other immunotherapy combinations, durvalumab + tremelimumab and nivolumab + ipilimumab, have also improved survival in phase 3 trials and are first-line options in the guidelines [9, 10, 11, 22].
The choice among these regimens depends on factors such as bleeding risk (especially esophageal varices if bevacizumab is used), autoimmune disease, liver function and the judgment of the treatment team [2, 3].
If the disease progresses after first-line treatment, drugs such as regorafenib, cabozantinib or ramucirumab (only in patients with an AFP of 400 ng/mL or higher) have prolonged survival after sorafenib [19, 23, 24], and after immunotherapy, lenvatinib or sorafenib is suggested [22].
Cholangiocarcinoma (bile duct cancer) at a glance
Cholangiocarcinoma arises from the cells of the bile ducts inside or outside the liver, and its treatment differs from that of hepatocellular carcinoma. In advanced disease, chemotherapy with gemcitabine and cisplatin plus an immunotherapy drug, pembrolizumab or durvalumab, is the standard first-line treatment [26] and has improved survival in phase 3 trials [16, 20]. The ESMO guideline recommends molecular testing of the tumor when drug treatment is started [26].
What should I do after a diagnosis?
Frequently asked questions
Frequently asked questions
I am a hepatitis B carrier. Will I definitely get liver cancer?
Can fatty liver disease also lead to cancer?
Is an AFP test alone enough for screening?
No. The main screening method is a liver ultrasound every 6 months, and AFP is used alongside it as a complement [2, 3]. Full answer: What is a tumor marker, and when is it useful? (Persian)
Who can have a liver transplant?
Transplantation is suitable for patients with limited tumors; the classic Milan criteria are a single tumor up to 5 cm, or up to 3 tumors each up to 3 cm [6]. Some centers also transplant under expanded criteria [2].
Evidence and recent advances (for physicians)
For physicians
Advanced disease: first-line therapy (BCLC C, and BCLC B unsuitable for locoregional therapy)
In IMbrave150 (501 patients), atezolizumab + bevacizumab reduced the risk of death compared with sorafenib (HR 0.58 in the primary analysis) [7]; in the updated analysis, median overall survival was 19.2 vs 13.4 months (HR 0.66) and median PFS 6.9 vs 4.3 months [8].
Tyrosine kinase inhibitors are recommended for patients who are not candidates for immunotherapy [2, 22]: in the SHARP trial (602 patients), sorafenib increased median overall survival from 7.9 to 10.7 months compared with placebo (HR 0.69) [17], and in the REFLECT trial lenvatinib was non-inferior to sorafenib, with median survival of 13.6 vs 12.3 months (HR 0.92) [18].
In HIMALAYA (1171 patients), the STRIDE regimen (a single dose of tremelimumab plus durvalumab every 4 weeks; doses in the regimens section) achieved a median overall survival of 16.43 vs 13.77 months with sorafenib (HR 0.78); durvalumab monotherapy was also non-inferior to sorafenib [9]. At 5-year follow-up, the OS HR was 0.76 and 60-month survival 19.6% vs 9.4% [10].
In CheckMate 9DW (668 patients, Child-Pugh 5 or 6), nivolumab + ipilimumab improved overall survival compared with lenvatinib or sorafenib (median 23.7 vs 20.6 months; HR 0.79; 36-month survival 38% vs 24%). Of note, the curves crossed early, with more deaths during the first 6 months in the immunotherapy arm (HR 1.65), and there were 12 treatment-related deaths vs 3; careful patient selection is therefore important [11].
Treatment after progression
In patients who had progressed on sorafenib, regorafenib increased median overall survival from 7.8 to 10.6 months compared with placebo in the RESORCE trial (573 patients) (HR 0.63) [19]. Cabozantinib increased median survival from 8.0 to 10.2 months in the CELESTIAL trial (707 patients) (HR 0.76) [23], and ramucirumab, in patients with AFP of 400 ng/mL or higher, increased median survival from 7.3 to 8.5 months in the REACH-2 trial (HR 0.71) [24]. The ESMO guideline suggests regorafenib or cabozantinib after sorafenib, and lenvatinib or sorafenib after first-line immunotherapy [22].
Intermediate disease: TACE combined with systemic therapy
In LEAP-012 (480 patients), TACE + lenvatinib + pembrolizumab improved progression-free survival (14.6 vs 10.0 months; HR 0.66), with far more grade ≥3 treatment-related adverse events (71% vs 32%) [13]; however, in the final analysis there was no difference in overall survival (median 40.4 vs 40.8 months; HR 0.98) [25]. In EMERALD-1 (616 patients), adding durvalumab + bevacizumab to TACE improved progression-free survival (15.0 vs 8.2 months; HR 0.77), whereas durvalumab without bevacizumab gave no significant benefit (HR 0.94) [12]. The ESMO guideline regards adding these combinations to TACE only as an option that “may be considered”, because their long-term benefit has not been established, and likewise regards TACE plus lenvatinib as an option when an immunotherapy combination is not possible [22]; TACE alone remains the standard treatment at this stage [5, 22].
Adjuvant therapy
In IMbrave050, atezolizumab + bevacizumab after resection or ablation in high-risk patients improved recurrence-free survival at the interim analysis (HR 0.72) [14]; however, this benefit was not sustained in the updated analysis (HR 0.90; 95% CI 0.72 to 1.12), and the authors concluded that the benefit–risk balance does not support adjuvant use of this combination [15]. The AASLD update regards close surveillance as the current standard after resection or ablation [21], and the ESMO guideline does not recommend adjuvant therapy with tyrosine kinase inhibitors or immunotherapy combinations [22].
Advanced biliary tract cancer
In the phase 3 KEYNOTE-966 trial (1069 patients), adding pembrolizumab to gemcitabine and cisplatin increased median overall survival from 10.9 to 12.7 months (HR 0.83) [20], and in the phase 3 TOPAZ-1 trial, adding durvalumab also improved overall survival (HR 0.80; estimated 24-month survival 24.9% vs 10.4%) [16]. The ESMO guideline recommends both combinations [26].
Treatment regimens and dosing (for physicians)
Treatment regimens and doses: index12 regimens
Esophageal varices (bevacizumab-containing regimens): because of the bleeding risk, screening for esophageal varices before starting atezolizumab + bevacizumab is strongly recommended in patients with portal hypertension [22]; in IMbrave150, assessment of varices within 6 months before treatment was mandatory [27], and grade 3 or 4 hypertension occurred in 15.2% of patients in the atezolizumab + bevacizumab group [7].
Immunotherapy (atezolizumab, durvalumab, tremelimumab, nivolumab, ipilimumab, pembrolizumab): monitor liver enzymes, creatinine and thyroid function at baseline and periodically thereafter; in regimens containing tremelimumab or ipilimumab, perform these tests together with ACTH at baseline and before each dose of these two drugs [27, 29, 30, 31, 32, 38]; with nivolumab + ipilimumab, also monitor ACTH periodically thereafter [31, 32]. Immune-related adverse events are managed according to severity by withholding or permanently discontinuing the drug (with corticosteroids if needed); dose reduction of atezolizumab, durvalumab, tremelimumab, nivolumab or pembrolizumab is not recommended [27, 29, 30, 31, 32, 38].
Gemcitabine and cisplatin (biliary tract cancer): refer to the labels of these drugs for dosing and dose modifications [30].
For physicians
Advanced hepatocellular carcinoma: first-line
Atezolizumab + bevacizumab (IMbrave150)
Unresectable or metastatic HCC, no prior systemic therapy; in the trial: Child-Pugh A and ECOG 0–1Cycle length: Every 21 days
Unresectable or metastatic HCC, no prior systemic therapy; in the trial: Child-Pugh A and ECOG 0–1 [7, 27]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Atezolizumab | 1200 mg (or 840 mg every 2 weeks or 1680 mg every 4 weeks) | IV; first infusion over 60 min, subsequent infusions over 30 min if tolerated | Day 1, before bevacizumab |
| Bevacizumab | 15 mg/kg | IV | Day 1, after atezolizumab |
IMbrave150 exclusion criteria: untreated or incompletely treated varices with a high risk of bleeding, variceal bleeding within the past 6 months, Child-Pugh B or C, moderate to severe ascites, history of hepatic encephalopathy, and autoimmune disease [27]. Stop bevacizumab at least 28 days before elective surgery and do not start it until 28 days after major surgery and until the wound has healed [28].
Bevacizumab monitoring: blood pressure every 2 to 3 weeks and periodic urine dipstick testing for proteinuria [28].
Modifications: dose reduction is not recommended for either drug; atezolizumab is withheld for grade 3 immune-related adverse events and permanently discontinued for grade 4 (for hepatitis with tumor involvement of the liver, separate ALT/AST thresholds are given in the label) [27]. Bevacizumab is withheld for proteinuria of 2 g or more per 24 hours until it falls below 2 g, and permanently discontinued for nephrotic syndrome, grade 3 or 4 hemorrhage, gastrointestinal perforation or hypertensive crisis [28].
Evidence: IMbrave150 (2022), IMbrave150 (2020)
Lenvatinib (REFLECT)
Unresectable HCC, first-line, particularly when immunotherapy is not suitable; in the trial: Child-Pugh A, ECOG 0–1Cycle length: Continuous
Unresectable HCC, first-line, particularly when immunotherapy is not suitable; in the trial: Child-Pugh A, ECOG 0–1 [18, 33]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Lenvatinib | Body weight 60 kg or more: 12 mg; body weight less than 60 kg: 8 mg (based on actual body weight) | Oral, with or without food | Once daily, continuous |
Dose-reduction levels: body weight 60 kg or more: 8 mg daily, then 4 mg daily, then 4 mg every other day; body weight less than 60 kg: 4 mg daily, then 4 mg every other day, then discontinue [33].
Monitoring: control blood pressure before starting, then measure it after 1 week, every 2 weeks for the first 2 months and at least monthly thereafter; proteinuria and liver tests before starting and periodically; monitor and correct electrolyte disturbances, and withhold for QTc greater than 500 ms [33]. For proteinuria of 2 g or more per 24 hours, withhold and resume at a lower dose; for nephrotic syndrome, gastrointestinal perforation or an arterial thromboembolic event, discontinue permanently [33]. In REFLECT, hepatic encephalopathy occurred in 8% of patients on lenvatinib (grade 3 to 5: 5%) [33].
Evidence: REFLECT (2018)
Sorafenib (SHARP)
Advanced HCC, first-line, when immunotherapy is not suitableCycle length: Continuous
Advanced HCC, first-line, when immunotherapy is not suitable [17, 34]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Sorafenib | 400 mg | Oral, on an empty stomach (1 h before or 2 h after a meal) | Twice daily, continuous |
Dose-reduction levels: 400 mg once daily, then 200 mg once daily or 400 mg every other day; if more than 2 dose reductions are needed, discontinue permanently [34].
Monitoring and discontinuation: regular liver tests; discontinue permanently for unexplained transaminase elevation (ALT grade 3 or higher, or AST/ALT more than 3 times the upper limit of normal with bilirubin more than 2 times), grade 2 or higher cardiac ischemia or infarction, bleeding requiring intervention, and gastrointestinal perforation; for QTc greater than 500 ms, withhold and correct electrolytes [34].
Evidence: SHARP (2008)
Durvalumab + tremelimumab (STRIDE regimen, HIMALAYA)
Unresectable HCC, no prior systemic therapy (BCLC C, or BCLC B unsuitable for locoregional therapy)Cycle length: Every 28 days
Unresectable HCC, no prior systemic therapy (BCLC C, or BCLC B unsuitable for locoregional therapy) [9, 29]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cycle 1, day 1 (once only) | |||
| Tremelimumab | 300 mg (body weight less than 30 kg: 4 mg/kg) | IV, 60-min infusion | Single dose; before durvalumab on the same day |
| From cycle 1 | |||
| Durvalumab | 1500 mg (body weight less than 30 kg: 20 mg/kg) | IV, 60-min infusion | Day 1, every 4 weeks |
No antiangiogenic agent; in HIMALAYA, endoscopy before enrollment was not mandatory, but patients with a history of variceal bleeding or at high risk of it required appropriate endoscopic treatment [30].
Durvalumab monotherapy (1500 mg IV every 4 weeks) was non-inferior to sorafenib in the same trial [9, 30].
Evidence: HIMALAYA (2025), HIMALAYA (2024), HIMALAYA (2022)
Nivolumab + ipilimumab (CheckMate 9DW)
Unresectable or metastatic HCC, no prior systemic therapy; in the trial: Child-Pugh A and ECOG 0–1
Unresectable or metastatic HCC, no prior systemic therapy; in the trial: Child-Pugh A and ECOG 0–1 [11, 31]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Induction: up to 4 doses | |||
| Nivolumab | 1 mg/kg | IV, 30-min infusion | Day 1, every 3 weeks |
| Ipilimumab | 3 mg/kg | IV, 30-min infusion | Day 1, immediately after nivolumab |
| Maintenance | |||
| Nivolumab | 240 mg every 2 weeks or 480 mg every 4 weeks | IV, 30-min infusion | After completion of the combination doses (in the trial: 480 mg every 4 weeks) |
The trial excluded patients with active autoimmune disease, hepatic encephalopathy within the past 12 months, platelets below 60,000, clinically significant ascites, or HBV and HCV (or HBV and HDV) coinfection; endoscopy before enrollment was not mandatory [31]. The excess of deaths in the first 6 months and the 12 treatment-related deaths in the combination arm make careful patient selection essential [11].
Evidence: CheckMate 9DW (2025)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Advanced hepatocellular carcinoma: after progression
Regorafenib (RESORCE)
Second-line after progression on sorafenib; patients who tolerated sorafenib (in the trial: Child-Pugh A, BCLC B or C)
Second-line after progression on sorafenib; patients who tolerated sorafenib (in the trial: Child-Pugh A, BCLC B or C) [19, 35]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Regorafenib | 160 mg (4 × 40-mg tablets) | Oral, after a low-fat meal | Once daily, days 1–21 |
RESORCE excluded patients who had stopped sorafenib because of toxicity or who could not tolerate 400 mg daily [35].
Boxed warning for hepatotoxicity: monitor liver function before and during treatment [35]. Dose reduction in 40-mg steps (120 mg, then 80 mg; lowest dose 80 mg); discontinue permanently for ALT/AST more than 20 times the upper limit of normal, ALT/AST more than 3 times with bilirubin more than 2 times, or intolerance of the 80-mg dose [35].
Evidence: RESORCE (2017)
Cabozantinib (CELESTIAL)
After prior sorafenib; in the trial: Child-Pugh ACycle length: Continuous
After prior sorafenib; in the trial: Child-Pugh A [23, 36]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cabozantinib (CABOMETYX tablets) | 60 mg | Oral, on an empty stomach (1 h before or 2 h after a meal) | Once daily, continuous |
Do not substitute cabozantinib capsules for CABOMETYX tablets. Dose reduction: 40 mg, then 20 mg daily; in moderate hepatic impairment (Child-Pugh B), the starting dose is 40 mg. Stop at least 3 weeks before surgery (including dental surgery) and do not start until 2 weeks after major surgery and until the wound has healed. With strong CYP3A4 inducers, increase the dose by 20 mg (maximum 80 mg) [36].
Ramucirumab (REACH-2)
After sorafenib (progression or intolerance) and only with AFP 400 ng/mL or higher; in the trial: Child-Pugh A, ECOG 0–1Cycle length: Every 14 days
After sorafenib (progression or intolerance) and only with AFP 400 ng/mL or higher; in the trial: Child-Pugh A, ECOG 0–1 [24, 37]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Ramucirumab | 8 mg/kg | IV; 60-min infusion, subsequent infusions over 30 min if tolerated | Day 1, every 2 weeks |
Premedication: an intravenous H1 antihistamine (e.g., diphenhydramine) before each infusion; after a grade 1 or 2 infusion-related reaction, add dexamethasone and acetaminophen [37].
Proteinuria: for 2 g or more per 24 hours, withhold until below 2 g and resume at 6 mg/kg (if it recurs, 5 mg/kg); for more than 3 g per 24 hours or nephrotic syndrome, discontinue permanently [37]. In REACH-2, hepatic encephalopathy and hepatorenal syndrome occurred in 6% of patients on ramucirumab vs 0% on placebo [37].
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Intermediate hepatocellular carcinoma: TACE plus systemic therapy (not approved)
TACE + lenvatinib + pembrolizumab (LEAP-012; not approved)
Unresectable, non-metastatic intermediate-stage HCC amenable to TACE; Child-Pugh A, ECOG 0–1Each drug’s schedule in the table
Unresectable, non-metastatic intermediate-stage HCC amenable to TACE; Child-Pugh A, ECOG 0–1 [13]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Lenvatinib | Body weight 60 kg or more: 12 mg; less than 60 kg: 8 mg | Oral | Once daily, continuous (21-day cycles) |
| Pembrolizumab | 400 mg | IV | Every 6 weeks, for up to 2 years (about 17 doses) |
| TACE | Per institutional protocol | Intra-arterial | Together with systemic therapy |
Improved progression-free survival but not overall survival, with far more grade ≥3 treatment-related adverse events; the ESMO guideline regards it only as an option that “may be considered” [13, 22, 25].
Evidence: LEAP-012 (2025)
TACE + durvalumab + bevacizumab (EMERALD-1; not approved)
Unresectable HCC without extrahepatic spread, amenable to TACE (1 to 4 TACE sessions within 16 weeks); Child-Pugh A to B7, ECOG 0–1
Unresectable HCC without extrahepatic spread, amenable to TACE (1 to 4 TACE sessions within 16 weeks); Child-Pugh A to B7, ECOG 0–1 [12]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| TACE period | |||
| TACE | 1 to 4 sessions per institutional protocol | Intra-arterial | All sessions within 16 weeks of the first TACE |
| Durvalumab | 1500 mg | IV | Every 4 weeks; first dose at least 7 days after the first TACE |
| After the last TACE | |||
| Durvalumab | 1120 mg | IV | Every 3 weeks; starting at least 14 days after the last TACE |
| Bevacizumab | 15 mg/kg | IV | Every 3 weeks, with durvalumab |
Upper endoscopy within 6 months before enrollment to assess varices and bleeding risk was mandatory [12]. Progression-free survival improved with durvalumab + bevacizumab, but durvalumab without bevacizumab gave no significant benefit; an overall survival benefit has not yet been shown, and the ESMO guideline regards it only as an option that “may be considered” [12, 22].
Evidence: EMERALD-1 (2025)
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Advanced biliary tract cancer: first-line
Gemcitabine + cisplatin + pembrolizumab (KEYNOTE-966)
Unresectable locally advanced or metastatic biliary tract cancer, no prior systemic therapy for advanced diseaseCycle length: Every 21 days
Unresectable locally advanced or metastatic biliary tract cancer, no prior systemic therapy for advanced disease [20, 38]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Pembrolizumab | 200 mg every 3 weeks (or 400 mg every 6 weeks) | IV | Day 1 |
| Gemcitabine | 1000 mg/m² | IV | Days 1 and 8, every 3 weeks |
| Up to 8 cycles | |||
| Cisplatin | 25 mg/m² | IV | Days 1 and 8, every 3 weeks |
Patients with autoimmune disease that required systemic treatment within the past 2 years, or who required immunosuppression, were excluded [38].
Evidence: KEYNOTE-966 (2023)
Gemcitabine + cisplatin + durvalumab (TOPAZ-1)
Unresectable locally advanced or metastatic biliary tract cancer, no prior systemic therapy (recurrence more than 6 months after surgery or adjuvant therapy allowed); ECOG 0–1
Unresectable locally advanced or metastatic biliary tract cancer, no prior systemic therapy (recurrence more than 6 months after surgery or adjuvant therapy allowed); ECOG 0–1 [16, 30]
Before prescribing: Shared safety notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Combination phase: up to 8 cycles | |||
| Durvalumab | 1500 mg (body weight less than 30 kg: 20 mg/kg) | IV, 60-min infusion | Day 1, every 3 weeks |
| Gemcitabine | 1000 mg/m² | IV | Days 1 and 8 |
| Cisplatin | 25 mg/m² | IV | Days 1 and 8 |
| Maintenance | |||
| Durvalumab | 1500 mg (body weight less than 30 kg: 20 mg/kg) | IV, 60-min infusion | Every 4 weeks |
Durvalumab is given before chemotherapy on the same day. Patients with ampullary carcinoma or with active or prior autoimmune disease were excluded from the trial [30].
Evidence: TOPAZ-1 (2022)
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Scientific evidence
Key studies
14 itemsSorafenib in advanced hepatocellular carcinoma
Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial
Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial
Transarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable, non-metastatic hepatocellular carcinoma (LEAP-012): a multicentre, randomised, double-blind, phase 3 study
Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial
Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma
Updated data from IMbrave050: Adjuvant atezolizumab plus bevacizumab for high-risk 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
Durvalumab with or without bevacizumab with transarterial chemoembolisation in hepatocellular carcinoma (EMERALD-1): a multiregional, randomised, double-blind, placebo-controlled, phase 3 study
Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer
Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma
Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial
Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma
Clinical guidelines
5 itemsPan-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 recommendations: The 2026 update
EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma
AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma
ESMO Clinical Practice Guideline interim update on the management of biliary tract cancer
References
38 referencesShow all references, 22 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.
- 1Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries
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- 6Liver Transplantation for the Treatment of Small Hepatocellular Carcinomas in Patients with Cirrhosis
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- 14Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial
- 15Updated data from IMbrave050: Adjuvant atezolizumab plus bevacizumab for high-risk hepatocellular carcinoma
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This page is based on reputable scientific sources and was last updated on 21 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.