A multicenter phase II study of donafenib in patients with advanced hepatocellular carcinoma.

Abstract

e15682 Background: In an early dose-escalation study, Donafenib, a new oral multikinase inhibitor, showed antitumor activity and favorable tolerability in treatment of different type solid tumors including HCC at both 0.2g bid and 0.3g bid dose levels. This prospective study aimed to evaluate the safety and efficacy of Donafenib in the patients with advanced HCC. Methods: In this phase 2 study, patients with unresectable HCC, who had Child-Pugh class A liver function and received no prior systemic therapy were enrolled across 10 sites in China. All patients received oral Donafenib 0.2g bid or 0.3g bid for several 4-week cycles, based on 1:1 randomization ratio. The radiology assessment was done every 8 weeks. The primary end points were safety and tolerability; secondary endpoints were time to progression assessed by an independent radiology committ, ORR , DCR, and PK. Results: Between June 17, 2014, and May 4, 2015, total 106 patients were enrolled and included in the safety analyses. Of them, 52 received donafenib 0.2g bid and 54 received 0.3g bid. The most common adverse events that led to dose discontinuation or reductions were hand-foot skin reaction in 10 (9.4%) patients (2 vs 8), liver dysfunction in 4 (3.8%) patients (1 vs 3), and leukopenia in 2 (1.9%) patients (1 vs 1). Other reported AEs caused dose reductions were hypertension, thrombocytopenia, throat ache, and cough. The median duration maintained for the initial dose was 90 and 72 days, respectively. The full analysis set for TTP includes104 patients (51and 53, respectively) and the per-protocol analysis set for ORR and DCR includes 84 patients (40 and 44, respectively). Median TTP was 111 days in 0.2g group compared with 110 days in 0.3g group (HR 0.99, 95% CI [0.62, 1.60]). At the Week 16, there were no complete responses in both groups, but partial response was confirmed in 4 (4.8%) patients (2 vs 2); and stable disease was in 35 (41.7%) patients (17 vs 18). Conclusions: Donafenib 0.2g bid and 0.3g bid were well tolerated. Significant adverse events were reported more frequently in 0.3g group. Both regimens showed similar treatment responses for patients with HCC, while 0.2g bid seems to be an appropriate first line therapeutic option for the treatment of HCC. Clinical trial information: NCT02229071.