Hepatocellular carcinoma

The EU has approved 11 indications of 10 drugs in hepatocellular carcinoma. 1 of them needs a biomarker result: AFP (1). 6 tumour-agnostic approvals also apply when the tumour carries the alteration.

Line of therapy

Approved indications, Hepatocellular carcinoma
DrugBiomarker requirementRegimenSettingConditions
AFP1
Serum AFP ≥ 400 ng/ml
Monotherapy
2L
advanced
After sorafenib
No biomarker required10
Atezolizumab
Tecentriq
None
+ bevacizumab
1L
advanced
No prior systemic therapy
Durvalumab
Imfinzi
None
+ tremelimumab
1L
advanced
None
Durvalumab
Imfinzi
None
Monotherapy
1L
advanced
None
None
+ nivolumab
1L
advanced
None
Lenvatinib
Lenvima
None
Monotherapy
1L
advanced
None
Nivolumab
Opdivo
None
+ ipilimumab
1L
advanced
None
None
+ durvalumab
1L
advanced
None
Cabozantinib
Cabometyx
None
Monotherapy
2L
Previously been treated with sorafenib
Regorafenib
Stivarga
None
Monotherapy
2L
Previously treated with sorafenib
Sorafenib
Nexavar
None
Monotherapy
Any line
None

Tumour-agnostic approvals6

Approved for any solid tumour that carries the alteration, wherever the tumour started.

DrugBiomarker requirementRegimenSettingConditions
EpCAM1
Monotherapy
2L
Malignant ascites; not eligible for further systemic anticancer therapy
HER21
Trastuzumab deruxtecan
Enhertuconditional
HER2-positive (IHC 3+)
Monotherapy
2L
advanced
After prior treatment; No satisfactory treatment options
NTRK fusion3
Entrectinib
Rozlytrekconditional
Monotherapy
Any line
No prior NTRK inhibitor; Older than 1 month; disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity; no satisfactory treatment options
Larotrectinib
Vitrakviconditional
Monotherapy
Any line
Locally advanced, metastatic or where surgical resection is likely to result in severe morbidity; no satisfactory treatment options
Repotrectinib
Augtyroconditional
Monotherapy
Any line
advanced
Prior NTRK inhibitor, or no prior NTRK inhibitor and treatment options not targeting NTRK provide limited clinical benefit or have been exhausted; Aged 12 years and older
RET fusion1
Monotherapy
Any line
advanced
Treatment options not targeting RET provide limited clinical benefit, or have been exhausted; Aged 2 years and older

Biomarkers in hepatocellular carcinoma

Label wording11

The sentence from section 4.1 of the SmPC that each indication above comes from.

  1. Nivolumab (Opdivo)
    OPDIVO in combination with ipilimumab is indicated for the first-line treatment of adult patients with unresectable or advanced hepatocellular carcinoma.
  2. Cabozantinib (Cabometyx)
    CABOMETYX is indicated as monotherapy for the treatment of hepatocellular carcinoma (HCC) in adults who have previously been treated with sorafenib.
  3. Durvalumab (Imfinzi)
    IMFINZI as monotherapy is indicated for the first line treatment of adults with advanced or unresectable hepatocellular carcinoma (HCC).
  4. Durvalumab (Imfinzi)
    IMFINZI in combination with tremelimumab is indicated for the first line treatment of adults with advanced or unresectable hepatocellular carcinoma (HCC).
  5. Atezolizumab (Tecentriq)
    Tecentriq, in combination with bevacizumab, is indicated for the treatment of adult patients with advanced or unresectable HCC who have not received prior systemic therapy (see section 5.1).
  6. Ipilimumab (Yervoy)
    YERVOY in combination with nivolumab is indicated for the first-line treatment of adult patients with unresectable or advanced hepatocellular carcinoma.
  7. Sorafenib (Nexavar)
    Nexavar is indicated for the treatment of hepatocellular carcinoma (see section 5.1).
  8. Lenvatinib (Lenvima)
    LENVIMA as monotherapy is indicated for the treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC) who have received no prior systemic therapy (see section 5.1).
  9. Regorafenib (Stivarga)
    - hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.
  10. Tremelimumab (Imjudo)
    IMJUDO in combination with durvalumab is indicated for the first line treatment of adults with advanced or unresectable hepatocellular carcinoma (HCC).
  11. Ramucirumab (Cyramza)
    Cyramza monotherapy is indicated for the treatment of adult patients with advanced or unresectable hepatocellular carcinoma who have a serum alpha fetoprotein (AFP) of ≥ 400 ng/ml and who have been previously treated with sorafenib.