Current approaches to incorporation of radium-223 in clinical practice

Abstract

Background: Treatment options for metastatic castration-resistant prostate cancer (mCRPC) have expanded in recent years and include cytotoxic agents (e.g., docetaxel and cabazitaxel), immunotherapy (e.g., sipuleucel-T), oral hormonal therapies targeting the androgen receptor axis (e.g., enzalutamide and abiraterone), and targeted alpha therapy (e.g., radium-223 dichloride (radium-223)). Although treatment guidelines have been updated to reflect the availability of new agents, it is not easy to apply them in daily clinical practice because recommendations vary depending on patient comorbidities and disease characteristics. Furthermore, therapeutic accessibility, clinical judgment, and experience affect the selection of treatment options.

Methods: In this review, we provide practical guidance for the integration of radium-223 into the management of patients with mCRPC based on our collective clinical experience, as well as the available clinical trial data.

Results: Radium-223 is a targeted alpha therapy; as a bone-seeking calcium mimetic, it accumulates in hydroxyapatite areas surrounding tumor lesions and selectively binds to the areas of increased bone turnover. Radium-223 prolongs overall survival and delays time to the first symptomatic skeletal events in men with mCRPC, and is indicated for the treatment of patients with CRPC, symptomatic bone metastases, and no known visceral metastases. We review its clinical efficacy and safety, practical guidance on identifying the appropriate patient, and recommendations for how best to educate and inform prospective patients regarding their treatment decision making. In addition, we review recent evidence for sequential and combination therapies with radium-223, provide our experiences with these treatment approaches, and discuss their implications for the future treatment of patients with mCRPC.

Conclusions: Based on our clinical experience, radium-223 should be considered relatively early in the treatment course in patients with mCRPC with bone metastases. Coordination of care among multidisciplinary team members, patients, and caregivers is essential for optimizing safe and effective treatment with all CRPC therapies.

Fig. 1. Prospective subgroup analysis of hazard ratios for death in the radium-223 ALSYMPCA trial [18]

The Eastern Cooperative Oncology Group (ECOG) scores the performance status of patients with respect to activities of daily living as follows: 0, fully active and able to carry out all predisease activities without restriction; 1, restricted in physically strenuous activity but ambulatory and able to carry out work of a light nature; 2, ambulatory and up and about for more than 50% of waking hours and capable of self-care but unable to carry out work activities; 3, capable of only limited self-care and confined to a bed or chair for more than 50% of waking hours; 4, completely disabled; and 5, dead. The category for use of opioids includes patients with a score of 2 or 3 on the World Health Organization “ladder” for cancer pain (a score of 1 indicates mild pain and no opioid use, 2 indicates moderate pain and occasional opioid use, and 3 indicates severe pain and regular daily opioid use). The category for non-use of opioids includes patients without pain or opioid use at baseline and patients with a score of 1 on the WHO ladder for cancer pain. Superscan refers to a bone scan showing diffuse, intense skeletal uptake of the tracer without renal and background activity. ALP denotes alkaline phosphatase, and NE not evaluated. Reproduced with permission from Parker et al. [18]