Results from the primary endpoint analysis in a phase III randomized, placebo-controlled study showed that intravenous radium Ra 223 dichloride (Xofigo), an alpha-particle-emitting radiotherapeutic agent and calcium mimetic that binds to newly formed bone stroma, significantly improved overall survival in castration-resistant prostate cancer patients with bone metastases.
San Diego-Results from the primary endpoint analysis in a phase III randomized, placebo-controlled study showed that intravenous radium Ra 223 dichloride (Xofigo), an alpha-particle-emitting radiotherapeutic agent and calcium mimetic that binds to newly formed bone stroma, significantly improved overall survival in castration-resistant prostate cancer (CRPC) patients with bone metastases.
Additional data from analyses of secondary endpoints showed that Ra 223, which was recently approved by the FDA for treatment of men with CRPC who have symptomatic bone metastases and no visceral disease, also had significant benefits for reducing pain and improving quality of life. These benefits were achieved with a favorable safety profile, including only a low incidence of myelosuppression, said co-author Nicholas J. Vogelzang, MD, of the study, which was presented at the AUA annual meeting in San Diego.
Dr. Vogelzang“Bone metastases are seen in more than 90% of men with CRPC and may cause severe pain that is often not relieved using current treatments. I believe Ra 223 will change the landscape for these patients,” said Dr. Vogelzang, professor of medicine at the University of Nevada School of Medicine and Comprehensive Cancer Centers of Nevada, Las Vegas.
Eligibility criteria for ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) required that men have a minimum of two bone metastases causing some pain, but not requiring morphine for symptom control. No visceral metastases were allowed, but patients could have lymph nodes up to 3 cm and small-volume lung nodules. They also had to have been treated previously with, refused, or considered unfit for docetaxel (Taxotere).
Baseline demographics for the 921 participants showed 40% of men had 20 or more metastatic bone lesions and 56% of men were at level 2 or higher on the World Health Organization pain relief ladder.
After stratification by alkaline phosphatase level as a marker for extent of bone metastases, bisphosphonates use, and prior docetaxel, men were randomized 2:1 to receive Ra 223, 50 kBq/kg or saline placebo. Six injections of assigned treatment were administered at 4-week intervals, and all patients also received best supportive care.
Treatment with Ra 223 conferred a striking survival advantage, prolonging overall survival by 3.6 months and reducing the risk of death by 30.5%. In addition, it significantly reduced the risk for needing external beam radiotherapy (EBRT) for pain by 33% and the need for opioids by 38%.
“At the time of this analysis, only about half of patients in either group needed EBRT. Median time to initial opioid use was 6.9 months in the placebo group but not yet reached for men treated with Ra 223,” Dr. Vogelzang said.
QoL results ‘consistently in favor of’ Tx
Quality of life changes were evaluated with The Functional Assessment of Cancer Therapy Prostate (FACT-P) questionnaire and analyzed responder rates, which required patients to achieve a specified change from baseline score. The results were consistently in favor of Ra 223 comparing responder rates for the total and subscale scores.
In the safety analysis, there was less toxicity with Ra 223 than with placebo except for slightly higher rates of hematologic adverse events, including neutropenia (5% vs. 2%) and thrombocytopenia (12% vs. 6%).
“One of the questions being asked about this agent is how many doses should men get. There was minimal bone marrow suppression with the six doses given in this trial, and so we think more can be given. How much more is the subject for clinical trial investigation,” Dr. Vogelzang said.
He added that how Ra 223 should be used with other agents recently made available for treatment of CRPC is also a subject of ongoing trials.
Dr. Vogelzang is a consultant and investigator for Algeta and Bayer Healthcare, and several of his co-authors are consultant/advisers, employees, and/or have an investment interest in Algeta and/or Bayer Healthcare.UT