This article is more than 5 years old. Information may no longer be current.
ORIENTAL study terminated due to failure of TSU-68 in interim analysis
Click Here to Manage Email Alerts
VIENNA — Clinicians stopped a trial of novel tyrosine kinase inhibitor TSU-68 in hepatocellular carcinoma after the drug failed to best placebo in overall survival in patients with hepatocellular carcinoma, according to findings presented at the 2015 International Liver Congress.
Joong-Won Park, MD, of the National Cancer Center Korea in Goyang, and colleagues suggested that transcatheter arterial chemoembolization (TACE) has been associated with incomplete tumor necrosis and tumor hypoxia. The novel oral TKI TSU-68 (Oratinib, Taiho Pharmaceutical Co.) inhibits VEGF and platelet-derived growth factor receptors.
The researchers assigned patients conventional TACE plus oral TSU-68 or placebo at 200 mg twice daily, with a dose modification of 200 mg every other day. Treatment was continued until TACE failure or unacceptable toxicity.
OS served as the primary outcome, while time to TACE failure, safety and biomarker analysis served as secondary endpoints. There were 889 patients included in the study. The final analysis included 444 patients in each treatment group.
At study termination, OS in the TSU-68 group was 31.1 months, compared with 32.3 months for placebo (P = .435). “Statistically, there was no difference,” Park said. “So this study was terminated by the interim analysis.”
The researchers observed a trend toward a longer median time to TACE failure in the TSU-68 group, 23.9 vs. 19.8 months (P = .245).
Stratified analysis results indicated that among patients with low VEGF-C, the median time to TACE failure was 25.5 months in the study drug arm and 18.4 months in the placebo arm. TSU-68 also benefitted patients with Barcelona Clinic of Liver Cancer stage-B disease in terms of prolonged time to TACE failure, 22.1 months vs. 14.9 months (P = .054).
Serious adverse events occurred in 48% of patients. Facial edema, peripheral edema and ascites were the most commonly reported adverse events in the study drug group. These events did not impact treatment duration of the study drug (332.0 days). There was one treatment-related death.
“TSU-68 combined with TACE did not improve OS in an interim analysis,” Park said. – by Rob Volansky
For More Information:
Park JW, et al. Abstract G06. Presented at: International Liver Congress; April 22-26, 2015; Vienna.
Disclosure: Park reports being a consultant for Taiho Pharmaceutical.