Combination of Radium-223 With Other Novel Agents in mCRPC

Jorge A. Garcia, MD, FACP: Let me just talk briefly about the combination of radium-223 with other novel agents, specifically radium-223 plus ABI [abiraterone], radium-223 plus enzalutamide, and radium-223 plus sipuleucel-T. There are a series of trials, some that have been completed, some have not, some have been fully presented, and some are not. The bottom line is with ABI specifically, the question oftentimes is how do you layer ABI with radium-223, or do you start them both together?

The most important piece of data, in my opinion, is the ERA 223 data which is the data that actually randomized men with metastatic castration-resistant disease to the combination of radium and ABI or ABI and placebo. Clearly that data did demonstrate that there was a significant increase in the skeletal-related or the skeletal symptomatic related events. Remember, the development to an SSE, which is symptomatic symptomatic event, is that it’s driven by a symptom, not by a film. When it’s SRE [skeletal-related event], usually it tends to be dictated by radiographic findings that lead to a symptom but they’re exactly the same—spinal cord compression, need for radiation therapy, orthopedic surgery for pathological fractures, and spinal cord compression.

When you look into that, I think the important part of this is 2-fold. With that data, I actually refrain of using the combination of radium-223 and ABI. But I also think there is a misperception of that data, and that data has been taken out of context. Some people have assumed that because radium-223 was used earlier, it would imply that radium-223 is not a treatment to be used earlier in the metastatic castration-resistant prostate cancer setting which is not what the trial tested. The trial was intended to test the combination of both agents against 1 agent alone, and that’s what we saw.

There is published data actually in the last year or two of ASCO [American Society of Clinical Oncology] meetings generally looking at enzalutamide. Although less SRE events were noted with ENZA [enzalutamide], trials cannot be compared head-to-head, but that also would imply maybe the importance of bone health agents which brings me to a very important point. I don’t use radium in combination with oral therapy at present time, and I’m intrigued to see what the final results of some of the data are with radium-223 and sipuleucel-T. That’s a fascinating combination, in my opinion, but hopefully will actually lead to some benefit to most men, and hopefully going to be able to utilize in the future. Obviously, we’re going to have to wait for that data to come out.

Transcript edited for clarity.

Case:A 69-Year-Old Man with Advanced Castrate Resistant Prostate Cancer

Initial presentation

• A 69-year-old man presented with intermittent back discomfort and loss of appetite
• PMH: hyperlipidemia controlled on a statin, no known family history of cancer
• PE: DRE revealed asymmetric, boggy prostate; otherwise unremarkable

Clinical Workup

• Biopsy with TRUS showed adenocarcinoma of prostate
  • Stage T2N0M0
  • Grade group 4
• Germline genetic testing: MLH1, MSH2, MSH6, PMS2, BRCA1/2, ATM, PALB2 and CHEK2
• Chest/abdominal/pelvic CT scan showed no evidence distant metastases or lymph node involvement
• Bone scan was negative
• PSA 24.9 ng/mL

Treatment and Follow-Up

• EBRT + ADT was started
• Follow up at 6 months, PSA 11.2 ng/mL
• At 12 months PSA 18.6 ng/mL
  • Patient reported increasing back discomfort and difficulty walking
  • Bone scan at that time showed multiple vertebral lesions at L3/L4
• Treatment with radium-223 dichloride was initiate
  • 6 infusions were completed, treatment was well tolerated