Radium-223 dichloride is a targeted alpha emitter that selectively binds to areas of increased bone turnover in bone metastases and emits high-energy alpha particles of short range (<100 m). As a bone-seeking calcium mimetic, radium-223 is bound into newly formed bone stroma, especially within the microenvironment of osteoblastic or sclerotic metastases. In the phase III ALSYMPCA trial, all patients had castrate-resistant prostate cancer with multiple bone metastases and had either progressed on docetaxel chemotherapy or were not candidates for docetaxel chemotherapy.23Patients were required to have 2 or more bone metastases and no known visceral metastases. Overall survival, the primary endpoint, was significantly improved compared with placebo (median 14.9 vs 11.3 months, HR = 0.70; 95% CI, 0.58 to 0.83). The 18-month survival was estimated to be 39% for the radium-223 group versus 29% for placebo. The time to first symptomatic skeletal event (which included the first use of external beam radiation therapy (RT) for symptom relief, new pathologic fracture, spinal cord compression, or tumour-related orthopaedic surgery intervention) was also significantly increased (median 15.6 vs 9.8 months, HR = 0.66; 95% CI, 0.52 to 0.83).
There have been no cost-effectiveness analyses on radium-223 performed using local cost data and Singaporean societal norms. The NICE Committee noted that the manufacturer's base case ICER for radium-223 compared with best supportive care was USD $85,118 per QALY gained and that the Committees adjustments to the model increased the base-case ICER to USD $88,008 per QALY gained (National Institute for Health and Care Excellence, Appraisal consultation document Radium-223 dichloride for treating hormone-relapsed prostate cancer with bone metastases; issue date: December 2014). However, it concluded that it was not possible to determine whether radium-223 could be considered a cost-effective use of National Health Service (NHS) resources, because the appropriate comparison with docetaxel and abiraterone had not been presented. At the time of publication of these guidelines, NICE has yet to publish their final recommendation on the use of radium-223 in patients with castrate-resistant prostate cancer.