Radium-223 Improves Survival in Advanced Prostate Cancer

Summary and Comment |
July 17, 2013

Radium-223 Improves Survival in Advanced Prostate Cancer

  1. Robert Dreicer, MD, MS, FACPAU1254

Overall survival and time to first symptomatic skeletal event were superior with radium-233 versus placebo.

  1. Robert Dreicer, MD, MS, FACPAU1254

Prior to the approval of docetaxel for advanced prostate cancer, the available beta-emitting radiopharmaceuticals strontium 89 and samarium were used to provide symptomatic benefit. Although these agents conferred some clinical benefit, they were associated with moderate-to-significant myelosuppresion. Radium-223 is an alpha-emitting, bone-seeking, calcium mimetic that binds into newly formed bone stroma. Such alpha-particle radiation induces potent double-stranded DNA breaks, yet the short path of these particles appears to spare surrounding marrow.

Now, international investigators have conducted an industry-sponsored, phase III trial in which 921 patients with castration-resistant, metastatic prostate cancer were randomized 2:1 to receive intravenous radium-223 or placebo every 4 weeks for 6 months. Patients had been treated with docetaxel, unless they were ineligible or unwilling to receive it.

The median overall survival (the primary endpoint) was longer with radium-223 group versus placebo (14.9 vs. 11.3 months; hazard ratio, 0.70; P<0.001); the survival benefit was consistent across all subgroups. Radium-233 recipients achieved a prolonged median time to first symptomatic skeletal event (15.6 vs. 9.8 months; HR, 0.66; P<0.001), defined as external-beam radiation therapy, symptomatic pathologic bone fractures, spinal cord compression, or tumor-related orthopedic surgical intervention. Radium-223 also resulted in fewer adverse events and low myelosuppression rates.

Comment

In May, the FDA approved radium-223 for use in men with castration-resistant, metastatic prostate cancer. The approval was silent on the timing of the agent's use, i.e., pre- or post-docetaxel. It is important to remember that this agent has no activity in patients with visceral disease, so appropriate patients should have the bulk of the disease in bone. Despite clear evidence of antitumor activity, only modest PSA declines were observed with radium-223 (only 16% demonstrated a >30% decline). The agent will need to be administered by either nuclear-medicine or radiation-oncology physicians, given the handling requirements. Radium-233's excellent safety profile sets the stage for a number of combination studies with other agents such as next-generation androgen-receptor–targeting agents.

Editor Disclosures at Time of Publication

  • Disclosures for Robert Dreicer, MD, MS, FACP at time of publication Consultant / Advisory board Dendreon; Eli-Lilly; Endo Pharmaceuticals; Ferring; Janssen; Millennium; Novartis Speaker's bureau Janssen Editorial boards Urology Leadership positions in professional societies National Cancer Institute (Co-Chair, GU Oncology Steering Committee)

Citation(s):

Reader Comments (1)

Shirley Cassada, M.D. Physician, Emergency Medicine, Key West, FL

When is the optimal time to begin chemotherapy if hormonal therapy (Lupron) still appears to be effective in Stage 4?

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