Donafenib improved overall survival (OS) when compared with sorafenib in Chinese patients with advanced hepatocellular carcinoma (HCC), according to a study published in the Journal of Clinical Oncology.

China has the highest global incidence of liver cancer, and the “diagnosis and treatment of HCC is a major public health concern in China,” the study authors wrote. OS results with sorafenib have proven inferior in Chinese patients, but no other monotherapy has outperformed sorafenib in a head-to-head comparison, the authors added.

With this in mind, the researchers conducted a phase 2-3 trial comparing sorafenib with donafenib, a multikinase inhibitor and deuterated sorafenib derivative, in Chinese patients with unresectable or metastatic HCC who had received no prior systemic therapy.

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The study enrolled 668 patients, and they were randomly assigned to receive donafenib or sorafenib twice daily until disease progression, severe toxicity, or treatment intolerance. The full analysis set included 328 patients in the donafenib arm and 331 patients in the sorafenib arm.

The median OS was significantly longer with donafenib than with sorafenib — 12.1 months and 10.3 months, respectively (hazard ratio [HR], 0.831; 95% CI, 0.699-0.988; P =.0245). The 18-month OS rate was 35.4% and 28.1%, respectively (P =.0460).

The median progression-free survival was 3.7 months in the donafenib arm and 3.6 months in the sorafenib arm (P =.0570). The objective response rate was 4.6% and 2.7%, respectively (P =.2448), and the disease control rate was 30.8% and 28.7%, respectively (P =.5532).

The most common drug-related adverse events (AEs) in both arms were hand-foot skin reactions and diarrhea. Both of these AEs were less frequent in the donafenib arm.

Grade 3 or higher drug-related AEs occurred in 38% of patients who received donafenib and 50% of patients who received sorafenib (P =.0018). The rate of AE-related treatment discontinuation was slightly lower in the donafenib arm than in the sorafenib arm — 10% and 13%, respectively (P =.3544).

“On the basis of these results, donafenib is likely to emerge as a new frontline standard for Chinese patients with advanced HCC; its safety and efficacy in other ethnic populations, and how it compares with other current systemic therapies for advanced HCC, such as atezolizumab/bevacizumab, will require further investigation,” the study authors wrote.

Disclosures: This research was supported by Suzhou Zelgen Biopharmaceuticals Co, Ltd. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Qin S, Bi F, Gu S, et al. Donafenib versus sorafenib in first-line treatment of unresectable or metastatic hepatocellular carcinoma: a randomized, open-label, parallel-controlled phase II-III trial. J Clin Oncol. Published online June 29, 2021. doi:10.1200/JCO.21.00163