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Donafenib in hepatocellular carcinoma
Rusi Chen1, Luca Ielasi1, Alma di Carlo2
1Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Abstract:
Hepatocellular carcinoma (HCC) is a global healthcare problem, with a high prevalence in nonindustrialized countries and a rising incidence in industrialized countries. Sorafenib demonstrated its efficacy as the first therapeutic agent for unresectable HCC in 2007. Since then, other multitarget tyrosine kinase inhibitors have demonstrated efficacy in HCC patients. Still, the tolerability of these drugs remains an unsolved problem, with 5-20% of patients permanently discontinuing their therapies due to adverse events. Donafenib is a deuterated form of sorafenib exploiting the increased bioavailability derived from the deuterium-for-hydrogen replacement. In the multicenter, randomized, controlled phase II-III trial ZGDH3, donafenib outperformed sorafenib in terms of overall survival, with favorable safety and tolerability. As a result, donafenib was approved as a possible first-line treatment of unresectable HCC by the National Medical Products Administration (NMPA) of China in 2021. In this monograph, we review the main preclinical and clinical evidence that emerged in the trials of donafenib.
Insights
Donafenib, a new drug for hepatocellular carcinoma (HCC), shows improved survival and better tolerability compared to sorafenib. This deuterated sorafenib offers a more effective first-line treatment option for unresectable HCC.
Area of Science:
- Hepatology and Oncology
- Drug Development
- Clinical Trials
Background:
- Hepatocellular carcinoma (HCC) presents a significant global health challenge.
- Existing treatments like sorafenib have limitations in tolerability, leading to therapy discontinuation.
- Donafenib offers a novel therapeutic approach for unresectable HCC.
Approach:
- A multicenter, randomized, controlled phase II-III trial (ZGDH3) evaluated donafenib against sorafenib.
- Donafenib is a deuterated form of sorafenib, designed for enhanced bioavailability.
- The study assessed overall survival, safety, and tolerability as primary endpoints.
Key Points:
- Donafenib demonstrated superior overall survival compared to sorafenib in HCC patients.
- The drug exhibited a favorable safety profile and improved tolerability.
- Donafenib received approval in China in 2021 as a first-line treatment for unresectable HCC.
Conclusions:
- Donafenib represents a significant advancement in the first-line treatment of unresectable HCC.
- Its improved efficacy and tolerability address key limitations of previous therapies.
- Further review of preclinical and clinical data supports donafenib's role in HCC management.
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