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Bayer HealthCare has announced that the FDA ( Food and Drug Administration ) has approved Xofigo ( Radium 223 dichloride ) for the treatment of patients with castration-resistant prostate cancer ( CRPC ), symptomatic bone metastases and no known visceral metastatic disease.
Xofigo is the first alpha particle-emitting radioactive therapeutic agent approved by the FDA that has demonstrated improvement in overall survival and delay in time to first symptomatic skeletal event compared to placebo, as shown in the pivotal Phase III ALSYMPCA trial.

Bone is the most common site in the body to be affected by metastatic cancer and bone metastases are particularly prevalent in patients with prostate cancer. Approximately 90% of patients with metastatic prostate cancer show evidence of bone metastases. Bone metastases can lead to an increase in frequency of skeletal events and have been shown to be the main cause of morbidity and death in patients with castration-resistant prostate cancer.

The approval of Xofigo is based on data from the pivotal Phase III ALSYMPCA ( ALpharadin in SYMptomatic Prostate Cancer ) trial. At the interim analysis, Radium 223 significantly improved overall survival [ hazard ratio, HR=0.695; p=0.00185 ]; median overall survival was 14.0 months with Radium 223 plus best standard of care versus 11.2 months with placebo plus best standard of care. Additionally, at the interim analysis there was a delay in the time to first symptomatic skeletal event for patients treated with Radium 223 vs placebo.

An updated analysis, conducted after the study was unblinded, showed a further improvement in overall survival for patients treated with Radium 223 vs placebo, with a median overall survival of 14.9 months vs 11.3 months ( HR=0.695 ).

The most common adverse reactions ( greater than or equal to 10% ) in patients receiving Radium 223 in the ALSYMPCA trial were nausea, diarrhea, vomiting and peripheral edema. The most common hematologic laboratory abnormalities ( greater than or equal to 10% ) were anemia, lymphocytopenia, leukopenia, thrombocytopenia and neutropenia.

Xofigo with the active ingredient Radium 223 dichloride is an alpha particle-emitting radioactive therapeutic agent with an anti-tumor effect on bone metastases. Radium 223 mimics calcium and forms complexes with the bone mineral hydroxyapatite at areas of increased bone turnover, such as bone metastases. The high linear energy transfer of alpha emitters may cause double-strand DNA breaks in adjacent cells, resulting in an anti-tumor effect on bone metastases. The alpha particle range from Radium 223 is less than 100 micrometers, which may limit damage to the surrounding normal tissue.

The ALSYMPCA trial was a Phase III, randomized, double-blind, placebo-controlled international study of Radium 223 dichloride with best standard of care vs placebo with best standard of care in symptomatic CRPC patients with bone metastases. The trial enrolled 921 patients in more than 100 centers in 19 countries. The study treatment consisted of up to six intravenous injections of Radium 223 or placebo each separated by an interval of four weeks.
The primary endpoint of the study was overall survival. A key secondary endpoint was time to first symptomatic skeletal event, as defined as external beam radiation therapy ( EBRT ) to relieve skeletal symptoms, new symptomatic pathologic bone fracture, occurrence of spinal cord compression, or tumor-related orthopedic surgical intervention.

Prostate cancer is the most common non-cutaneous malignancy in men worldwide. In 2008, an estimated 899,000 men were diagnosed with prostate cancer and 258,000 died from the disease worldwide. Prostate cancer is the sixth leading cause of death from cancer in men.
A majority of men with castration-resistant prostate cancer have radiological evidence of bone metastases. Once the cancer cells settle in the bone, they interfere with bone strength, often leading to pain, fracture and other complications that can significantly impair a man’s health. Bone metastases secondary to prostate cancer typically target the lumbar spine, vertebrae and pelvis. In fact, bone metastases are the main cause of morbidity and death in patients with castration-resistant prostate cancer.

Source: Bayer HealthCare, 2013

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