Randomized phase II study of axitinib versus placebo plus best supportive care in second-line treatment of advanced hepatocellular carcinoma

Regional Differences in Efficacy, Safety, and Biomarkers for Second-Line Axitinib in Patients with Advanced Hepatocellular Carcinoma: From a Randomized Phase II Study

“…Although the study did not meet its primary endpoint of overall survival (OS), improvements favoring the axitinib/BSC arm were observed in progression-free survival (PFS), time to tumor progression, and the clinical benefit rate, especially among Asian patients. Furthermore, an exploratory analysis indicated a longer OS with axitinib/BSC than with placebo/BSC when patients who were intolerant to prior antiangiogenic therapy were excluded from the data set [7]. The safety profile in patients with metastatic HCC was as expected based on prior studies of axitinib in RCC, with no new safety signals or unexpected toxicities.…”

“…NCT01210495) of axitinib/BSC versus placebo/BSC in patients previously treated with antiangiogenic therapy for locally advanced or metastatic HCC were analyzed in this study. The details of the study design and patient eligibility criteria have been reported previously [7]. In brief, patients with confirmed HCC who progressed on or were intolerant to one prior antiangiogenic therapy, with Child-Pugh class A liver function, and with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 were stratified by tumor invasion (presence vs. absence of extrahepatic spread and/or vascular invasion) and geographic region (non-Asia vs. Asia) and randomly assigned in a 2: 1 ratio to axitinib/BSC or placebo/BSC.…”

“…As described previously [7], the randomized patients received axitinib or placebo orally at a starting dose of 5 mg twice daily in 4-week cycles. The axitinib or placebo dose could be increased to 7 mg twice daily, and then to a maximum of 10 mg twice daily, if patients tolerated the drug without any treatment-related adverse events (AEs) of grade >2 for 2 consecutive weeks and were normotensive.…”

“…Based on the antitumor activity of agents inhibiting the VEGF/VEGFR signaling pathway observed in HCC in clinical studies and the nonclinical activity of axitinib in HCC animal models, the efficacy and safety of axitinib in combination with best supportive care (BSC) was compared with placebo plus BSC (placebo/ BSC) in patients with locally advanced or metastatic HCC following failure of one prior antiangiogenic therapy in a global randomized phase II study conducted in 2010-2012 [7]. Although the study did not meet its primary endpoint of overall survival (OS), improvements favoring the axitinib/BSC arm were observed in progression-free survival (PFS), time to tumor progression, and the clinical benefit rate, especially among Asian patients.…”

Regorafenib as Second-Line Systemic Therapy May Change the Treatment Strategy and Management Paradigm for Hepatocellular Carcinoma

“…1). The benefit of excluding patients intolerant to sorafenib was demonstrated in the subanalysis of a previous phase II study of axitinib, which generated an excellent HR and a significant study outcome [15,16].…”