Experience with regorafenib in the treatment of hepatocellular carcinoma
Alessandro Granito1, Antonella Forgione2, Sara Marinelli2
1Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Via Albertoni 15, Bologna, 40138, Italy.
Abstract:
Regorafenib is a diphenylurea oral multikinase inhibitor, structurally comparable to sorafenib, which targets a variety of kinases implicated in angiogenic and tumor growth-promoting pathways. Regorafenib was the first agent to positively show significant survival advantage as a second-line therapy in patients with unresectable hepatocellular carcinoma (HCC) who had previously failed first-line treatment with sorafenib. Recent evidence has shown that its antitumor efficacy is due to a comprehensive spectrum of tumor neo-angiogenesis and proliferation inhibition and immunomodulatory effects on the tumor microenvironment, which plays a crucial role in tumor development. This review addresses the rationale and supporting evidence for regorafenib's efficacy in HCC that led to regorafenib's approval as a second-line therapy. In addition, we review proof from clinical practice studies that validate the RESORCE trial results. We discuss regorafenib's potential role in the newly emerging therapeutic strategy based on combination with immune checkpoint blockade and its possible extensibility to patient categories not enrolled in the registrative study.
Insights
Regorafenib offers a survival advantage for advanced hepatocellular carcinoma (HCC) patients after sorafenib failure. Its efficacy stems from inhibiting tumor growth, angiogenesis, and modulating the immune microenvironment.
Area of Science:
- Oncology
- Pharmacology
- Cancer Biology
Background:
- Regorafenib is a multikinase inhibitor structurally similar to sorafenib.
- Hepatocellular carcinoma (HCC) is a significant global health concern.
- Second-line treatment options for advanced HCC after sorafenib failure were limited.
Purpose of the Study:
- To review the evidence supporting regorafenib's efficacy in unresectable HCC.
- To validate RESORCE trial findings with clinical practice data.
- To explore regorafenib's role in combination therapies and new patient populations.
Main Methods:
- Review of clinical trial data, including the RESORCE trial.
- Analysis of real-world evidence from clinical practice studies.
- Exploration of preclinical and clinical data on combination strategies.
Main Results:
- Regorafenib demonstrated a significant survival advantage in second-line HCC treatment.
- Its efficacy is attributed to inhibiting angiogenesis, proliferation, and immunomodulatory effects.
- Clinical practice data supports the RESORCE trial findings.
Conclusions:
- Regorafenib is an established second-line therapy for advanced HCC.
- Its multifaceted mechanism of action contributes to its antitumor activity.
- Future research should focus on combination therapies and expanded indications.
