The Potential of Radium-223 as a Treatment in mCRPC

treatment for prostate cancer

Michael Morris, MD

From its approval in May 2013 to recently being considered as a combination treatment with other drugs, radium-223 dichloride (Xofigo) shows great potential in positively impacting treatment for metastatic castration-resistant prostate cancer (mCRPC), according to Michael Morris, MD, medical oncologist, Memorial Sloan Kettering Cancer Center.

"This drug has been shown to prolong survival and improve quality of life in men with mCRPC. It improves overall survival; therefore, it helps patients live longer. It also delays complications related to bone metastases, known as SSE. These include bone fracture, bone pain, spinal cord compression, and others. Nevertheless, the drug is not only helping patients live longer, but it is helping them live better, as well," said Morris in an interview with Targeted Oncology.

Radium-223 was initially the first alpha-emitting radiopharmaceutical approved by the FDA for treatment of patients with mCRPC with bone metastases. The approval was based on the phase III ALSYMPCA trial, which showed an overall survival (OS) rate of 14 months for patients who received radium-223, compared with the 11.2 month OS in patients who received placebo.

Following the trial, an international expanded access program (EAP) examined 696 patients with bone mCRPC. Patients received concomitant therapy,. Of those receiving the therapy, 22% received on abiraterone acetate (Zytiga), 20% on denosumab, 18% on bisphosphonates, and 4% on enzalutamide (Xtandi), in addition to radium-223.

At the time of analysis, median OS was 16 months, and medium time to first symptomatic skeletal-related event (SSE) was 18 months. Ad hoc analysis found that OS was statistically significantly longer in patients with concomitant denosumab and concomitant abiraterone. Based on the results of this trial, combination treatments with radium-223 are now being considered.

Morris said radium-223 in combination with other drugs may very well be the future of the treatment.

"Combining radium-223 with other types of treatment that directly target the cancer may be the future, whether that is androgen receptor—directed therapy, chemotherapy, or novel therapeutics that are yet to be developed. There is currently a study of radium-223 and abiraterone," he said. "There is also a study of radium-223 with chemotherapy that is under discussion that we hope to open shortly. In terms of new therapeutics, radium-223 is a DNA-damaging agent, and there is new data showing that patients that have BRCA2 mutations are very responsive to PARP inhibitors. Therefore, there is an idea to give radium-223 with a PARP inhibitor."

Morris said the concept of radiopharmeceuticals has been around for a long time, though the main difference between previous radiopharmaceuticals and radium0223 is that previous bone-seeking radiopharmaceuticals admitted a particle of energy known as a beta particle rather than an alpha particle. He added that the benefit of alpha particles is that they a more shallow tissue penetration, fewer side effects, and prolong survival for patients.

"Radiopharmaceuticals deliver targeted radiation therapy to either the tumor itself or compartments that contain the tumor. The whole idea behind a bone-seeking radiopharmaceutical is that it targets the component of the body that contains the primary site of metastatic disease, which, in prostate cancer, is the bone," he said "It delivers radiation therapy to the bone, and since that is where most of the prostate cancer has localized, it is in turn treating most of the metastatic compartment of the disease. It delivers a very specific type of radiation therapy to the bone, which is an alpha-emitting radiation therapy or alpha particle. This has unique characteristics that minimize toxicity while maximizing treatment effect."

Morris said despite the optimism, there is still research being done on how to properly utilize raidium-223.

"Work is also still being done on optimizing how to administer radium-223 alone, how frequently patients should receive it, how long, and at what dose. All of those things are still being refined and optimized, and there are various clinical trials looking at those questions. Over the next few years, we should have more information regarding optimization of the drug alone and how to sequence or combine it with other drugs," he said.