Liver cancer is the second most common causes of cancer death worldwide. According to the WHO GLOBOCAN 2012, there are approximately 782,000 new cases and approximately 746,000 deaths annually. Liver cancer also ranked 2nd of TOP 10 cause of death in Taiwan causing 8,000 deaths annually according to statistics from Taiwan’s Ministry of Health and Welfare. Liver resection and radiofrequency ablation (RFA) remain to be common medical procedures for liver cancer. However, the major cause of death is tumor recurrence.
Bayer’s Nexavar® was approved by USFDA and EMA in 2007 for treatment of advanced-stage liver cancer. But its usage for treating early stage (about 30%) and intermediate stage (about 45%) liver cancer has not been approved by USFDA. Hence, there is unmet need for adjuvant therapy in preventing liver cancer recurrence after liver resection.
PI-88 is a mixture of oligosaccharides mimicking heparan sulfate that antagonizes angiogenic growth factors (VEGF, FGF-1, and FGF-2) and blocks heparanase from cleaving heparan sulfate in the extracellular matrix (ECM). PI-88 has successfully accomplished with phase I and II clinical studies in compliance with USFDA guidelines, and demonstrated good safety profiles and promising efficacy in counteracting liver cancer. Having owned the global commercialization rights of PI-88, MBC has initiated phase III clinical study and have now completed the recruitment of subjects in Taiwan, Korea, China, and Hong Kong.
Liver cancer recurrence after curative treatment adversely influences clinical outcome, with a 5-year cumulative recurrence rate above 70%. In our phase II trial published in J Hepatol (vol: 50, 958-968, 2009), the study group received 160 mg/day of PI-88 showed a reduction of recurrence rate from 50% to 37% at the end of 12 months. The recurrence free survival extends from 27 weeks to 48 weeks at 70 percentile.
MBC conducted an observational follow-up study in order to track patient outcomes up to 2 years after the previous phase II trial. Results revealed that the clinical benefits of PI-88 at 160mg/day were maintained for more than two years with minimal AE after only the initial 36 weeks of active treatment. Subgroup analyses on high-risk patients with single tumor ≥2cm (or multiple tumors) and positive HBV or HCV infection conferred statistically significant survival advantage.
“A Prospective, Randomized, Double-blind, Placebo controlled, Parallel-group, International Multicenter Phase III Trial Of PI-88 In the Adjuvant Treatment Of Subjects With Hepatitis Virus Related Hepatocellular Carcinoma After Surgical Resection” abbreviated as PATRON is designed for Phase III study. This study is to confirm the efficacy and safety of PI-88 in the adjuvant treatment of viral hepatitis related liver cancer after curative surgery. We have now completed the recruitment of subjects in Taiwan, Korea, China, and Hong Kong for PATRON.