Updated data from the Phase III ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial for investigational drug Alpharadin (radium-223 dichloride) confirm its overall survival benefit in men with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases compared to the interim analysis from June 2011.
The updated data showed that radium-223 dichloride improved overall survival by 44% (p=0.00007, HR=0.695), resulting in a 30.5% reduction in the risk of death compared with placebo.
The median overall survival benefit with radium-223 dichloride was 2.8 months at the time of the interim analysis in June 2011 and 3.6 months in this updated analysis (14.9 months in patients given radium-223 dichloride vs 11.3 months with placebo).
These data will be presented as a late-breaking abstract in an oral abstract session on June 5, 2012 at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, IL (USA) (LBA No. 4512).
“Bone metastases are one of the main causes of disability and death in patients with castration-resistant prostate cancer, yet until now there has been little progress made towards developing therapies that target the cancer when it has spread to the bone,” said Dr. Chris Parker of The Royal Marsden NHS Foundation Trust, London, and The Institute of Cancer Research, London, and principal investigator of ALSYMPCA.
“Radium-223 dichloride is the first therapy specifically addressing prostate cancer that has spread to the bone that has shown in a Phase III trial to significantly improve overall survival.”
In addition to improving overall survival, radium-223 dichloride led to a statistically significant delay in time to first skeletal-related event (SRE).
The overall safety and tolerability profile for radium-223 dichloride was consistent with previous study results. The most common haematologic adverse events included anaemia (31% vs. 31%), neutropenia (5% vs. 1%) and thrombocytopenia (12% vs. 6%) for patients receiving radium-223 dichloride compared with those receiving placebo.
With respect to Grade 3 and 4 adverse events, the most common events included anaemia (13% vs. 13%), neutropenia (2% vs. 1%) and thrombocytopenia (6% vs. 2%).
The most common non-haematologic adverse events included bone pain (50% vs. 62%), nausea (36% vs. 35%), diarrhoea (25% vs. 15%), and vomiting (19% vs. 14%) for patients receiving radium-223 dichloride as compared to placebo. With respect to Grade 3 to 4 adverse events, the most common events included bone pain (21% vs. 26%).
“These updated ALSYMPCA data showing continued improvement in overall survival with Alpharadin (radium-223 dichloride) are very encouraging, because they bring us one step closer to providing additional hope for men who are fighting prostate cancer at its most aggressive stage,” said Kemal Malik, MD, Member of the Bayer HealthCare Executive Committee and Head of Global Development.
“Radium-223 dichloride showcases Bayer’s commitment in developing innovative treatments for patients for whom there are limited options.”
Radium-223 dichloride was granted Fast Track designation by the U.S. Food & Drug Administration (FDA). The Fast Track process is designed to facilitate the development, and expedite the review, of drugs to treat serious diseases and fill an unmet medical need. Fast Track designation must be requested by the drug company and can be initiated at any time during the drug development process.
Bayer plans to file radium-223 dichloride for CRPC with regulatory authorities based on the ALSYMPCA data in the second half of 2012. In terms of further development activities, Bayer intends to conduct studies in earlier settings of prostate cancer, including combination studies with other agents, as well as undertaking exploratory studies in other tumours such as breast cancer and osteosarcoma.