Treating mCRPC Patients With Radium 223

Jorge Garcia, MD:Obviously, we at Cleveland Clinic have been 1 of the groups that actually has the most experience around the United States using radium 223. As I said before, I think there are some challenges with this agent. In our opinion, at least in my personal opinion, radium 223 ideally should be given earlier rather than later. I think patient phenotype remains to be defined. I look at my patients, and if I do believe that those patients can actually endure at least 4 to 6 months of continuous therapy without me feeling that they’re going to progress clinically or radiographically, then I think decide they may be an ideal patient for radium 223.

I also believe that it totally depends on the sequence of events and how you actually present that data to the patients. But I think when you look at the safety profile of radium 223, obviously the beauty of an alpha emitter compared with the older beta emitters in the past is you have a short penetrance. You don’t impact the marrow in the production of red cells, white cells, and platelets as much as we used to with older agents. So you may not have that degree of myelosuppression that we have concerns with from the older agents. And I think when you look at the safety profile, for instance, you have to consider the likelihood of developing grade 3 and grade 4 events. You have to look at the significant suppression of platelets, white blood cell counts, and red blood cells. The difference between prechemotherapy patients, meaning chemotherapy-naïve, and postchemotherapy patients is not really that drastic. I don’t think that should be the excuse not to use it. I think you believe in the agent, and you believe in the ability of the decision to make people live longer. But you have to explain to the patient how and why you’re selecting this treatment.

Again, I would just tell physicians and practitioners in the country that, ideally, you want to expose your metastatic castration-resistant prostate cancer patients to all life-prolonging agents. And I would argue that the sequence of those choices will be totally dependent on how the patients have been treated from the get-go, meaning from the original presentation. So your sequence may actually change. But I would like to believe that all patients with castration-resistant prostate cancer should be able to receive all the agents that we have shown have the ability to make them to live longer.

Transcript edited for clarity.

Case: Met HSPCa Progressing to mCRPC

June 2016

H&P

• A 64-year old gentleman referred to a medical oncologist with lower back pain
• Initial work-up included:
  • PSA of 79.5 ng/ml
  • WBS showing 3 bone metastasis — 1 Right pelvic area and 2 in lumbar spine
  • CT Chest/Abdomen and Pelvis showed no pelvic lymph nodes and no evidence of visceral disease
  • TRUS/Bx revealed adenocarcinoma of the prostate gland with a Gleason score of 9 [5+4]
• PMH: HTN, Hyperlipidemia - both controlled on oral medications and a family history of colon cancer
• His KPS is 90% and the remaining of his blood work is unremarkable

Pt was started on ADT with LHRH agonist-based therapy and abiraterone + prednisone. He also was placed on monthly zoledronic acid.

• During therapy minimal AEs that included G1 fatigue, hot flashes and muscle aches
• Nadir PSA at 6 months was 0.9 ng/mL

August 2017

• Despite a Testosterone level < 50 ng/dL, patients PSA began to rise
  • PSA August 1.56 ng/mL
  • PSA November 4.4 ng/mL
  • Patient remain completely asymptomatic

February 2018

• Patient is complaining of new back pain (L spine radiating to right hip area) for which he takes over the counter NSAIDs
• PSA now is 6.5ng/mL
• Repeat WBS and CT C/A/P demonstrated 2 new lesions in L spine. No epidural disease or fractures and no evidence of visceral disease.
• Patient is diagnosed as minimally symptomatic Metastatic castration-resistant and abiraterone + prednisone was discontinued.
• Radium 223 therapy was initiated — 6 cycles were completed with improvement of bone pain and minimal AEs that included G1 fatigue and G1 anemia.
  • PSA during therapy ranged from 6.5 to 8.9ng/mL

September 2018

• Patient now is experiencing anorexia, fatigue and progressive abdominal pain
• WBS showed stable disease however CT C/A/P now showed progressive liver metastases
• PSA is now 10.7 ng/ml
• Hemoglobin is 10 g/dL, ANC is 3900 and Platelets are 331,000
• Normal Liver function tests (ALT/AST, Alk Phos, TBili) and LDH of 565

Patients is started on Docetaxel-based chemotherapy (75mg/m2 on 21-day cycles)

Patient completes 6 cycles of therapy with expected AEs including G1 fatigue, G1 alopecia and G1 peripheral neuropathy. His scans at the completion of chemotherapy showed SD with tumor burden reduction in liver lesions and SD in bones. His Hemoglobin level at the completion of chemotherapy is 12.1 g/dL and his ANC and platelets are also within normal limits.