Therapeutic Options for mCRPC

Jorge A. Garcia, MD, FACP: The standard of care for men with metastatic castration-resistant prostate cancer has evolved drastically over the last decade or more. We now have plenty of agents that we can use in the context of this situation. I would argue that you can pocket these treatments into oral therapy, chemotherapy, and radiopharmaceuticals.

In this context of where the patient in the given case stands, the standard of care with existing data could be, in fact, to initiate the patient with oral therapy. There are a series of agents that can be actually used in this context. We have the PREVAIL data, And we also have the COU-AA-302 data that supported and led to a registration of agents such as abiraterone acetate or the androgen receptor inhibitor, enzalutamide. Either of these 2 agents would have been a viable option for this patient.

The second bucket that 1 can think of for managing this patient could be cytotoxics. Docetaxel remains the frontline cytotoxic agent of choice for most men with metastatic castration-resistant disease. I would argue that we move away from the need for symptoms to be able to document the use of docetaxel. For many years, the NCCN [National Comprehensive Cancer Network] Guidelines restricted docetaxel to people with symptomatic disease. Finally we moved away from that. If you look at and remember the historical data that led to FDA approval of docetaxel, specifically TAX 327 and the SWOG 9916, those 2 trials did not actually mandate for people to have symptomatic disease. It was just whether you have metastatic castration-resistant disease, regardless of symptoms.

This particular patient could be a candidate for oral therapy. The second bucket for patients such as him could be initiating docetaxel-based chemotherapy. The third bucket, which I forgot to mention earlier, could be the use of immunotherapy. The IMPACT trial is the trial that randomized patients like him with metastatic castration-resistant disease to either sipuleucel-T or placebo. It clearly demonstrated a survival improvement in favor of sipuleucel-T. This could be another solid option for this patient, just by virtue of the outcome improvement. I can dissect a little more why one might pick 1 over the other in a bit.

The fourth bucket that you can think of obviously would be radiopharmaceuticals. This is where radium 223 dichloride perhaps comes into play. Maybe it is the reason, to some extent, why whoever was treating this patient elected to use radium 223 as a radiopharmaceutical. Radium 223 was also approved in the United States several years back by virtue of the ALSYMPCA data, a trial that was mostly conducted in the European region. The trial mainly included those with symptomatic metastatic castration-resistant disease. But if you really dissect the data, a little less than half the patients were not taking opioid medications for pain control. If you have a bucket of patients who are not taking opioids, they are what we used to call in the PREVAIL and the COU-AA-302 studies as perhaps asymptomatic or minimally symptomatic metastatic castration-resistant patients.

But the important point is that the ALSYMPCA trial demonstrated that if you add radium 223, which is an alpha emitter for this patient population compared with placebo, plus the best supportive care at the time when that trial was conducted, there’s a survival benefit in favor for those who received radium 223. Those are some of the buckets of treatment patients can use or physicians should be thinking of using when you see someone with metastatic castration-resistant disease, even in the minimally or symptomatic space.

How you dissect which is the best option, how you sequence the treatments, and how you layer these options remains controversial. I don’t think we really know if oral therapy is better than chemotherapy as a frontline agent for these patients because that data have not been prospectively validated. The reality is that most of us in the US setting probably would try a patient like this on an oral agent first, but the data with ALSYMPCA would certainly support the use of radium 223 for this particular patient.

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