Improving the Prognosis for Patients With mCRPC

Daniel J. George, MD:We’re learning more and more that there are a lot of biologic differences between abiraterone and enzalutamide. Even though these drugs target the same pathway, they do so in very different mechanisms. One’s given with a glucocorticoid, chronically, for a long period of time. We’re not doing that in the other setting.

When I think about the ERA 223 data, it’s important to recognize that this was done in the context of abiraterone and prednisone, not in the context of enzalutamide. The PEACE III trial really looks at this in a similar disease setting but with a very different agent. I think that’s a really critical piece.

There’s 1 other aspect to the PEACE III trial that’s really critical: the timing. The timing in the PEACE III trial is for the hormonal therapy, the enzalutamide, to be added first. Then, 3 months later, the radium-223 is given. That window of time may be fundamentally different from what was done in ERA 223. Again, ERA 223 was not done as our standard of care. That was done in a much earlier disease setting in asymptomatic or minimally symptomatic disease—at the very initiation of these hormonal therapies. That may have a different biologic context to the bone and noncancer environment versus in patients who have gone through treatment for a number of months and stabilized that circumstance.

So, again, I think there are enough differences between enzalutamide and abiraterone-prednisone—between the timing of these agents and what we know now. Importantly, in PEACE III, all of these patients are really encouraged to take bone strengthening agents as concomitant support. I think all of those differences could result in a very different outcome from what we see with ERA 223, and that’s what we need to know.

The most important thing to probably take away from what we just covered is: Don’t be afraid to treat your patients. Don’t be afraid to treat your patients who have a performance status of 0 or 1. Don’t be afraid to treat your patients with multiple, different treatment options in sequence or in layering. What you should be afraid of is these patients dying from this disease, which, for the vast majority of the patients, will happen within 2 to 4 years of being diagnosed with metastatic castrate-resistant disease. That may seem like a long time, but during that last 6 months there’s no treatment. Their performance status is 2 or worse during their last 6 months. If there is treatment for these patients, it’s not helping.

So, we have a tighter window to treat our patients than we frequently realize in these patients who have a performance status of 0 or 1. They may have had a long natural history of disease up to this point, but the biology of castration-resistant metastatic disease is different. So, treat your patients. Treat them in sequence or in layering. Don’t be afraid to be proactive in using these agents. Treat in a multidisciplinary manner. When giving radium-223, I don’t write for that drug. That’s something that I have other specialists do. They’re involved. That’s why I say this is multidisciplinary.

The same thing happens with chemotherapy for our urologists. This is a partnership. This is not “OK, now the patient’s yours.” This is a partnership. These patients have long-standing relationships with their urologists. They have long-standing urinary issues that need to be continued to be managed. They’re going to look to those physicians for guidance during treatment decisions. Who actually gives the drug? The nurses do. None of us actually give the drug.

So, we need to think about management as a team. Palliative care—we’ve probably underutilized palliative care in many of these patients. Don’t think of palliative care during the last 3 months. Think of palliative care as preventive care. What are the things that we want to be doing so that we can continue treatment in these patients and get their performance statuses back up? This is really critical.

Think about bone health. Bone health is probably one of the complications that can lower performance status to the point that we can’t treat these patients any more. Preventing that, not at the time of those complications but 3 to 5 years earlier, is really critical. Thinking about bone health early on in their hormone therapy is a really important piece. Many urologists are excellent at this, but we’re all human. We all need these reminders. None of us are perfect. This is a great opportunity for us to really look back and say, “How can we really improve the life and extension of life for these patients?”

Transcript edited for clarity.

mCRPC Treated With Radium-223 Therapy

January 2015

H&P:

• A 71-year old gentleman presented with urinary incontinence
• Past medical history: HBP controlled with lisinopril
• On digital rectal examination prostate was enlarged
• Patient was asymptomatic

Imaging:

• Transrectal ultrasound and biopsy revealed adenocarcinoma of the prostate gland with a Gleason score 9 [4+5] with 9 of 12 cores positive
  • PSA, 10.2 ng/mL
• CT scan was negative for metastases
• He was started on a 3-month depot injection of leuprolide 22.5 mg and treated with 7800 cGy IMRT

April 2016

• Patient returned for 3-month injection; his PSA level increased to 47 ng/mL
  • CT/Bone scans were negative for metastases
• He was started on enzalutamide
  • PSA, 12 ng/mL

October 2016

• 6 months later the patient complained of severe fatigue and lower back pain
  • Imaging with CT and bone scan showed multiple metastases of the spine and pelvis
  • PSA levels increased to 76 ng/mL
  • ALP, 268 U/I
• Radium-223 therapy was initiated in addition to continuing enzalutamide
• After 3 infusions of radium-223
  • PSA declined to 31 ng/mL
  • ALP decreased to 80 U/l
  • CT scan showed no new bone metastases
  • Fatigue decreased, and patient’s physical activity increased