CHICAGO, IL USA (UroToday.com) - Dr. Tanya Dorff, assistant professor of medicine at the University of Southern California, gave an update on data directing timing of radium-223 in the treatment of men with prostate cancer that has metastasized to bone. She reviewed that radium-223 acts as a calcium-mimetic, traveling to bone metastases because these are areas of active bone turnover that normally incorporate calcium. The side effect profile includes effects on hematopoiesis, and although some men do experience transiently low blood counts, most do not experience profound bone marrow suppression. Blood counts typically normalize within a month, allowing for monthly dosing of up to 6 doses.
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To review which patients may benefit most from treatment with radium-223, Dr. Dorff discussed ALSYMPCA. This was a phase III trial that randomized men with metastatic castration-resistant prostate cancer (mCRPC) with symptomatic bone metastases to treatment with monthly radium-223 vs best supportive care. Men in the study had already received docetaxel (58%), were ineligible for docetaxel, or refused treatment with chemotherapy. In addition to reducing pain in the patients treated with radium-223, treatment was associated with a prolongation in overall survival of approximately 3.6 months (HR = 0.69). Men included in the study had a heavy burden of disease, with 40% having > 20 bone metastases and 54% using opioids for pain control. In subgroup analyses, men with higher alkaline phosphatase (≥ 220 U/L) and with higher numbers of metastatic disease (other than those with a superscan) appeared to have greater survival benefit from treatment. Men with < 20 metastatic sites had less need for palliative external beam radiation also. Men with lower alkaline phosphatase (< 220 U/L) also benefitted, as they had prolonged time to symptomatic skeletal related event (12.2 months vs 6.7 months for ≥ 220 U/L; HR 0.64, 95% CI 0.52-0.78).
In terms of timing, Dr. Dorff discussed several key points. First, she noted that controlling disease in the bone before it becomes extremely widespread may confer an advantage. Recent data suggests that radium-223 can be safely given concurrently with other treatments, including enzalutamide, abiraterone acetate, and even docetaxel. Given this, earlier combination treatment may be feasible, safe, and potentially may control the disease more effectively. The side effect profile of radium-223 is tolerable, making it easy to use at any point in the disease continuum, even in minimally symptomatic men. Hematologic toxicity can be greater if radium-223 is given after prior treatment with docetaxel chemotherapy, though the overall rate of grade 3 or 4 toxicities is relatively low. Additionally, if radium-223 is used after failure of abiraterone or enzalutamide, fewer men complete 4 or more cycles of therapy. Finally, men treated with radium may require less subsequent treatment with external beam radiation, sparing the patient both toxicity and cost.
Dr. Dorff also explored reasons that might encourage later use of radium-223. First, if used too early, patients may not experience profound reduction in pain because they have less widespread disease and less pain to start out with. If used later, the treatment can have a more profound effect due to the greater disease burden in the bone. Additionally later use may ultimately lead to greater uptake and delivery of radium to the bone due to more areas of bone turnover and drug incorporation. Late utilization of radium-223 would reduce the risk of patients developing secondary malignancies. Finally, later use may lead to reduced overall cost of treatment. Men treated with radium-223 after docetaxel had 8 fewer hospital days per patient per year, while men treated before docetaxel had only 4.6 fewer hospital days per patient per year compared with untreated patients.
At present there is no clear data suggesting that treatment earlier or later with radium-223 is ideal. Dr. Dorff’s presentation revealed pros and cons to either approach. In any event, the current data suggests that radium-223 appears to be safe to use in combination with other therapies. It also failed to find a single biomarker or set of biomarkers that defines an ideal patient population who benefits most from treatment. Until further work is done, the optimal timing of treatment with radium-223 will depend on availability of various treatments, and patient and physician preferences.
Presented by Tanya Dorff, MD at the American Society of Clinical Oncology (ASCO) Annual Meeting - Illumination & Innovation: Transforming Data into Learning - May 29 - June 2, 2015 - Chicago, Illinois USA
USC Norris Comprehensive Cancer Center and Hospital, Los Angeles, CA USA
Reported by Alicia K. Morgans, MD, assistant professor of medicine and medical oncologist at Vanderbilt-Ingram Cancer Center, and medical writer for UroToday.com