The Changing Management of Prostate Cancer-Radium 223 Dichloride (Xofigo) Targets Bone Metastases

Prostate cancer is the most common solid organ tumor in men. According to the American Cancer Society, in 2013:

• about 238,590 new cases of prostate cancer will be diagnosed in the United States
• about 29,720 men will die of prostate cancer

Prostate cancer occurs mainly in older men, with the average age at diagnosis of 67 years. Nearly two-thirds of cases are diagnosed in men 65 years or older, and it is rare before age 40 years. Even though it is the most common form of solid organ cancer, affecting about 1 in 6 men over a lifetime, prostate cancer is the second-leading cause of cancer death in American men, behind lung cancer.¹

Androgen deprivation therapy (ADT) is the main treatment for advanced prostate cancer, and generally considered first line for these patients. This therapy provides temporary relief of symptoms, and can even reduce tumor size and levels of prostate-specific antigen (PSA) in most men.

Patients being managed with ADT who have evidence of disease progression (increasing serum PSA, new clinical metastases, progression of existing metastases) are considered to have castration-resistant prostate cancer (CRPC). Until recently these patients had limited options. However, in the last 2 years, contemporary research as led to the development and marketing of multiple agents that improve overall survival in these men. These newer treatments include agents that interfere with androgenic stimulation of prostate cancer growth (abiraterone, enzalutamide), taxane chemotherapy (docetaxel, cabazitaxel), immunotherapy (sipuleucel-T), and now a bone-targeted radiopharmaceutical (radium 223 dichloride).

Most patients with CRPC have radiologic evidence of bone metastases. When the cancer establishes itself in the bone, it ultimately can affect bone strength. These patients often have significant pain and are generally more vulnerable to fractures and other complications, which can have significant health implications. Prostate cancer that spreads to the bone usually targets the lumbar spine, pelvis, and vertebrae. The main cause of disability and death among those with CRPC is bone metastases.

On May 15, 2013, the US Food and Drug Administration (FDA) approved radium 223 dichloride (Xofigo) for the treatment of patients with castration-resistant prostate cancer who have bone metastases without any known visceral metastatic disease. Radium 223 dichloride is a radiotherapeutic agent that emits alpha particles. The drug mimics calcium and forms complexes with hydroxyapatite at areas of increased bone turnover, such as bone metastases.

The approval was based on a double-blind, randomized, placebo-controlled trial in patients with metastatic castration-resistant prostate cancer who had symptomatic bone metastases and no known visceral metastatic disease (ALSYMPCA). The patients were randomized to receive radium 223 dichloride, intravenously, every 4 weeks for 6 cycles plus best standard of care (N = 541) or a matching placebo plus best standard of care (N = 268). In this trial, best standard of care included local radiotherapy, corticosteroids, anti-androgens, estrogens, estramustine, or ketoconazole. All patients were to continue androgen deprivation therapy. Overall survival (OS) was the primary end point.²

The trial results showed a statistically significant improvement in OS. The median OS was 14.0 months for patients treated with radium 223 dichloride and 11.2 months for patients treated with placebo. The improvement in OS was supported by a delay in time to first symptomatic skeletal event for patients treated with radium 223 dichloride.² Radium 223 dichloride is the first alpha particle—emitting radioactive therapeutic agent approved by the FDA that has demonstrated improvement in overall survival.

Health Plan Perspective

Prostate cancer, and in particular CRPC, now has multiple treatment options that generally did not exist 2 years ago. These treatment options, however, come at a price:

• Provenge: $93,000 for a standard course of 3 treatments.
• Cabazitaxel: The typical 6 cycles cost about $50,000.
• Abiraterone: An 8-month course of treatments costs about $47,000.
• Enzalutamide: A typical eight-month treatment costs nearly $60,000.
• Xofigo: As of this writing the price has not been announced.

Payers are therefore bracing for increased cost to treat these patients, many of whom will undoubtedly be tried on 1 or more of these new agents. The dilemma for plans that attempt to manage this category is that there are virtually no comparative data on the relative effectiveness of these treatments, and no data on which drug will be best suited for which patient. Until such time as these data become available, payers will not likely be able to manage this category in any meaningful way. With the potential for sequencing these agents and even the possibility of combination therapy, the potential cost of treating these patients will likely continue to increase. In the meantime, plans will be left with the relatively blunt instrument of managing access to these agents based on FDA indications and compendium recommendations. Clearly there is a need for additional research in this area that can help both physicians and payers better target the right therapy for the right patient with CRPC.

1. American Cancer Society. Prostate cancer key statistics. http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-key-statistics. Accessed May 20, 2013.

2. National Cancer Institute. FDA approval for radium 223 dichloride. http://www.cancer.gov/cancertopics/druginfo/fda-radium-223-dichloride. Accessed May 20, 2013.