Survival Benefit Shown With Investigational Alpha-Emitting Radiopharmaceutical in Men With Hormone Resistant Metastatic Prostate Cancer

STOCKHOLM, SWEDEN — An investigational drug that emits alpha radiation achieved a significant improvement in overall survival (OS), as well as delayed time to first skeletal-related event (SRE) in a Phase III trial of men with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases.

“Radium-223 chloride [Alpharadin™] improved survival and time to SREs and was very well tolerated. If approved, this drug is likely to become standard of care,” stated Chris Parker, MD, Royal Marsden Institute in Surrey, UK. “This is the first drug targeted to bone metastases in prostate cancer that has been shown to improve survival. Other drugs targeted to the bone treat symptoms,” he added. Parker presented this talk at a Presidential Session on the best abstracts at the 2011 European Multidisciplinary Cancer Congress (ECCO/ESMO/ESTRO).

“Injectable radium-223 targets goe to new areas of bone formation, such as cancer metastasis, and emits alpha particles, which are highly damaging and short range. The tumor cells are killed, but the more distant cells in the bone marrow are spared,” he continued. “Only a few hits are required with radium-223, whereas with beta radiation [used in radiopharmaceuticals], thousands of hits are needed and there is damage to the surrounding tissue.” Treatment with radium-223 takes 5 minutes and is done on an outpatient basis.

The ALSYMPCA international Phase III study enrolled 922 men at more than 100 centers in 19 countries with hormone-refractory prostate cancer and multiple, symptomatic bone metastases. Patients were randomized 2:1 to either radium-223 plus current standard of care, or placebo plus current standard of care. Radium-223 was delivered via injection 1 out of every 4 weeks for 6 cycles. Sham injections were used in the placebo group.

At the first interim analysis, a survival benefit was seen favoring radium-223 and the trial was stopped early in 2010. Median overall survival (OS) was 14 months in the radium-223 arm versus 11.2 months in placebo patients (P=.000185). Median time to first skeletal related event (SRE) was 13.6 months versus 8.4 months, respectively (P=.00046), representing a 64% improvement with the alpha-emitting agent. Other findings were normalization of alkaline phosphatase in 33% of men treated with radium-223 versus 1% of placebo patients, and a 49% improvement in time to PSA progression (P=.00015).

Radium-223 was extremely well tolerated, Parker noted. Grades 3 and 4 hematologic toxicities were: anemia, 11% with radium-223 versus 12% with placebo; neutropenia, 2% versus 1%, respectively; and thrombocytopenia, 4% versus 2%, respectively. The most common nonhematologic adverse events in both groups were bone pain, nausea, diarrhea, constipation, and vomiting.

Although quality of life data were collected in ALSYMPCA, they have not yet been analyzed, Parker said, but a Phase II trial suggested that radium-223 improved bone pain.

The FDA has granted radium-223 Fast Track status. Bayer Health Care plans to file a New Drug Application for the drug in mid-2012. Parker had no information on what the cost of radium-223 will be, if approved. “It will be competitive with all new cancer drugs, I would think. They are all expensive,” he said.