Donafenib improves OS vs sorafenib in Chinese patients with advanced HCC

Donafenib, a novel small-molecule multikinase inhibitor and a deuterated derivative of sorafenib, has been shown to improve overall survival (OS) vs sorafenib as first-line treatment in Chinese patients with advanced hepatocellular carcinoma (HCC).

In a randomized, open-label, parallel-controlled phase II–III trial, 668 patients with unresectable or metastatic HCC and a Child-Pugh score ≤7 who had received no prior systemic therapy were recruited from 37 sites across China. The patients were randomized in a 1:1 ratio to receive oral donafenib (0.2 g) or sorafenib (0.4 g) BID until disease progression or intolerable toxicity. [J Clin Oncol 2021;doi:10.1200/JCO.21.00163]

In the full analysis set (FAS) of 659 patients (donafenib, n=328; sorafenib, n=331; median age, 53 years in both arms; male, 86 percent vs 88 percent), the primary endpoint of OS was significantly improved with donafenib vs sorafenib (median, 12.1 months vs 10.3 months; hazard ratio [HR], 0.831; 95 percent confidence interval [CI], 0.699 to 0.988; p=0.0245). OS rate at 18 months was 35.4 percent vs 28.1 percent (p=0.0460).

“A trend of superior OS with donafenib vs sorafenib was consistently observed across most predefined subgroups and statistically significant improvement in OS was achieved in some subgroups in the FAS,” the investigators reported.

In the intention-to-treat (ITT) population, OS results were similar and in favour of donafenib vs sorafenib (median, 12.0 months vs 10.1 months; HR, 0.839; 95 percent CI, 0.706 to 0.996; p=0.0309).

Progression-free survival did not differ significantly between the donafenib and sorafenib arms in the FAS (median, 3.7 months vs 3.6 months; HR, 0.909; 95 percent CI, 0.763 to 1.082; p=0.0570).

Objective response rate was 4.6 percent in the donafenib arm vs 2.7 percent in the sorafenib arm (p=0.2448), with complete response achieved in 0.3 percent vs none of the patients and partial response achieved in 5.8 percent vs 3.6 percent of the patients. The disease control rate was 30.8 percent vs 28.7 percent (p=0.5532).

Grade ≥3 drug-related adverse events (AEs) were reported in significantly fewer patients in the donafenib vs sorafenib arm (38 percent vs 50 percent; p=0.0018). Drug-related AEs led to dose interruption and reduction in 25 percent vs 36 percent of the patients (p=0.0025), and to treatment discontinuation in 6 percent vs 8 percent of the patients (p=0.3544). AEs resulted in death in 2 percent vs 4 percent of the patients (p=0.1610).

“Donafenib demonstrated superiority over sorafenib in terms of OS and has a favourable safety and tolerability profile in Chinese patients with advanced HCC, showing promise as a potential first-line monotherapy for these patients,” the investigators concluded.