NEW YORK (Reuters Health) – Donafenib, a novel multikinase inhibitor and a deuterated sorafenib derivative, significantly improved overall survival versus sorafenib in first-line treatment of patients with advanced hepatocellular carcinoma (HCC) in a phase-2/3 trial conducted in China.
“Donafenib is the first monotherapy agent to achieve superior overall survival results over sorafenib in patients with unresectable or metastatic HCC and presented improved safety and tolerability, rendering it a new option for the first-line treatment of advanced HCC,” write Dr. Shukui Qin with the Cancer Centre of Bayi Hospital, Nanjing Chinese Medicine University, and colleagues in the Journal of Clinical Oncology.
“Liver cancer is one of the most common cancers worldwide and in China,” they point out. “China has the highest global incidence, accounting for more than half of the new cases and deaths caused by liver cancer in the world.”
Sorafenib is a standard first-line treatment for advanced HCC in China and until now, no other single-agent therapy has shown better overall survival outcomes.
Dr. Qin and colleagues evaluated the efficacy and safety of first-line donafenib versus sorafenib in 668 Chinese patients with advanced HCC, a Child-Pugh score of 7 or less, and no prior systemic therapy.
The patients were randomly assigned to receive oral donafenib (0.2 g) or sorafenib (0.4 g) twice daily until intolerable toxicity or disease progression.
Median overall survival was significantly longer with donafenib than sorafenib treatment (12.1 vs. 10.3 months; hazard ratio, 0.83; 95% confidence interval: 0.699 to 0.988; P=0.02).
Median progression-free survival was 3.7 months with donafenib and 3.6 months with sorafenib (P=0.06). The objective response rate was 4.6% and 2.7%, respectively (P=0.24), and the disease-control rate was 30.8% and 28.7% (P=0.55).
“Donafenib also exhibited a better safety and tolerability profile than sorafenib, consistent with early clinical studies of donafenib,” the study team says.
Treatment-related adverse events (AEs) of grade 3 or higher occurred in significantly fewer patients taking donafenib than sorafenib (38% vs. 50%; P=0.0018). “A lower frequency of grade ≥ 3 AEs with donafenib contributed to improved patient adherence and decreased levels of drug interruption and discontinuation,” the researchers report.
“On the basis of these results, donafenib is likely to emerge as a new frontline standard for Chinese patients with advanced HCC,” Dr. Qin and colleagues say.
They note that the safety and efficacy of donafenib in other ethnic populations, and how it compares with other current systemic therapies for advanced HCC such as atezolizumab/bevacizumab, needs to be studied.
Dr. Augusto Villanueva, a liver-cancer expert at the Icahn School of Medicine at Mount Sinai, in New York City noted that when this trial started, sorafenib was the only drug approved in the first-line for HCC.
“Since then we’ve had the combination of atezolizumab plus bevacizumab in the first-line, which proved to be superior to sorafenib. The ideal trial would test donafenib against the combination of atezolizumab plus bevacizumab,” Dr. Villanueva, who was not involved in the research, told Reuters Health by phone.
The study was sponsored by Suzhou Zelgen Biopharmaceuticals Co, Ltd. One author is an employee of the company.
SOURCE: https://bit.ly/3B1aWE6 Journal of Clinical Oncology, online June 29, 2021.
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