Clinical Cases in Advanced Prostate Cancer - Episode 6

Case 1: Therapy Selection for Nonmetastatic CRPC

December 21, 2020
Targeted Oncology

Experts in genitourinary oncology share their methods and patient specific factors that aid in selecting therapy for nonmetastatic castration-resistant prostate cancer.

Jorge A. Garcia, MD, FACP: Patrick, obviously we believe M0 CRPC [nonmetastatic castration-resistant prostate cancer] is a space that doesn’t really exist and basically is a virtue of lack of great imaging. Remind our audience of the new label for PSMA [prostate-specific membrane antigen], at least the restricted label right now that we have in the country with the UCLA [University of California, Los Angeles] and UCSF [University of California, San Francisco] group. Is the M0 CRPC that we see in this case, a true M0?

Patrick G. Pilié, MD: The recent approval of the Gallium-68 PSMA PET [positron emission tomography] scan would fit in this patient’s case. It’s for patients with biochemical recurrence with concern for distant metastatic disease. It’s more sensitive than the CT scans and bone scan. And as we see this implemented more and more in the community, we might find a large portion of these patients who we are calling M0 castrate-resistant prostate cancer might actually have M1 or low-burden M1 disease.

Jorge A. Garcia, MD, FACP: I think you raise a good point. Mary-Ellen stated earlier that we didn’t know the true impact of the shift in the natural history of someone’ disease, and whether or not, if we were to find some metabolic activity in PSMA with whichever metabolic agent, if that would translate into a rapid therapeutic intervention and, therefore, a true change in outcome. This brings me to the next question. Mary-Ellen, you are seeing this patient, M0 CRPC, with whatever technology you use. You know he has bad disease from the beginning. What are your treatment options? How do you think of this patient, and what makes you think one treatment or the other one?

Mary-Ellen Taplin, MD:The first question I ask myself is, “Is this somebody I want to treat?” If you remember, the phase 3 trials used a PSA [prostate-specific antigen] doubling time of I believe 9 or 10 months to be eligible. This patient’s PSA doubling time was 8 months. So, No. 1, I would consider him for treatment. Then I would look across the FDA-approved options, which include apalutamide and darolutamide, and select one of them. There are no data that guide us to select one over the other.

My read of the results is that darolutamide is a little better tolerated in terms of fatigue, rash, and perhaps even hypertension. I generally try to put in a prescription and see what the copay is for darolutamide for my patients in this situation.

Jorge A. Garcia, MD, FACP: That’s great. Ganesh, it is fair to say that our group today works in environments where urologists often do not keep those patients with rising PSA from the beginning, so our access to these M0 CRPCs is quite common. It is also fair to say that these patients oftentimes sit in urology offices across America. How do you see the use of 3 oral, novel androgen receptor inhibitors in the urology space as we see it right now with the existing data?

Ganesh V Raj, MD, PhD:In our practice, I do the same. I hold on to these prior patients. When you operate on a patient, you have an affinity for them, and they have an affinity for you and they tend to stay with you. So I treat these patients for a fair bit of time. One of the key questions, especially with M0 and M1 CRPC, is what is the right next treatment? And truth be told, there are no real data to guide us, especially no comparative data. If you look at the overall improvement in survival for each of these drugs, it’s almost superimposable.

One of the key things we look at is the [adverse] effect profile. The profound fatigue with apalutamide and enzalutamide cannot be understated. The patients are found to have a significant amount of fatigue. We’ve been impressed with the fact that with darolutamide, the patients aren’t as fatigued. That’s not to say there is no fatigue, but it’s a relative degree of it. This is not something we use alone to decide. The only 2 decision points are whether we get insurance approval for whichever drug and what the out-of-pocket cost would be. These are real things we look at for patients. Secondly, if they can be on darolutamide and they can get it done, we put them on that.

Transcript edited for clarity.