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Review
. 2024 Jan;19(1):115-123.
doi: 10.1007/s11523-023-01026-9. Epub 2024 Jan 18.

Tremelimumab: A Review in Advanced or Unresectable Hepatocellular Carcinoma

Nicole L France  1 , Hannah A Blair  2
Affiliations
Review

Tremelimumab: A Review in Advanced or Unresectable Hepatocellular Carcinoma

Nicole L France et al. Target Oncol. 2024 Jan.

Erratum in

Abstract

Tremelimumab (tremelimumab-actl; Imjudo®) is a monoclonal antibody and immune checkpoint inhibitor (ICI) that blocks cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). A single, priming dose of intravenous tremelimumab is used in combination with durvalumab, an ICI that blocks programmed cell-death ligand 1, in a regimen known as STRIDE (Single Tremelimumab Regular Interval Durvalumab). STRIDE is approved for the treatment of adults with unresectable hepatocellular carcinoma (HCC) in the USA and Japan and for the first-line treatment of adults with advanced or unresectable HCC in Europe. In the phase III HIMALAYA trial, STRIDE significantly improved overall survival (OS) compared with sorafenib in adults with unresectable HCC and no prior systemic therapy. A higher proportion of STRIDE versus sorafenib recipients had an objective response to treatment. The OS benefit associated with STRIDE was sustained with 4 years' follow-up. STRIDE had a manageable safety profile that differed from that of sorafenib. Grade 3 or 4 treatment-related adverse events occurred in a lower proportion of STRIDE versus sorafenib recipients. Based on the available evidence, tremelimumab used as part of the STRIDE regimen is a valuable first-line agent that expands the treatment options available to patients with advanced or unresectable HCC.

Plain language summary

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a leading cause of cancer death worldwide. HCC is commonly associated with cirrhosis linked to chronic viral hepatitis and non-alcoholic fatty liver disease. Tremelimumab (tremelimumab-actl; Imjudo®) is a type of immunotherapy that helps the body’s immune system attack HCC cells by binding to and blocking the action of an immune-checkpoint protein called cytotoxic T lymphocyte-associated antigen-4. A single dose of intravenous tremelimumab is used in combination with treatment with durvalumab, in a regimen known as STRIDE (Single Tremelimumab Regular Interval Durvalumab), for adults with unresectable HCC in the USA and Japan and as a first-line treatment for adults with advanced or unresectable HCC in the EU. In patients with unresectable HCC, STRIDE improved overall survival more than sorafenib, including at 4 years’ follow-up. A higher proportion of patients responded to treatment with STRIDE compared with sorafenib. STRIDE had manageable adverse events. Tremelimumab used as part of the STRIDE regimen is a valuable first-line agent that expands the treatment options available to patients with HCC that is advanced or unable to be removed with surgery.

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Conflict of interest statement

Nicole L. France and Hannah A. Blair are salaried employees of Adis International Ltd/Springer Nature, and declare no relevant conflicts of interest. All authors contributed to this article and are responsible for its content.

Figures

Fig. 1
Fig. 1
Most common treatment-related adverse events occurring in ≥ 10% of patients in any treatment arm in the safety analysis population of the phase III HIMALAYA trial [11]. PPE palmar-plantar erythrodysesthesia syndrome, STRIDE Single Tremelimumab Regular Interval Durvalumab, ϕ zero value
Fig. 2
Fig. 2
Grade 3 or 4 treatment-related adverse events occurring in ≥ 2% of patients in any treatment arm in the safety analysis population in the phase III HIMALAYA trial [11]. ALT alanine aminotransferase, AST aspartate aminotransferase, PPE palmar-plantar erythrodysesthesia syndrome, STRIDE Single Tremelimumab Regular Interval Durvalumab, ϕ zero value
See this image and copyright information in PMC

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