PARP Inhibitors in Prostate Cancer - Episode 6

Advances in Metastatic Castration-Resistant Prostate Cancer

A specialist describes the advances being made in metastatic prostate cancer and provides some clinical pearls for community oncologists.

Matthew Fowler: Lastly, I want to focus in on treatment considerations and future directions. Is patient access a factor in considering the best treatment?

Oliver Sartor, MD: Absolutely. I hate to say it, but 1 thing we’re always dealing with is the ability for insurance to pay for the drugs; they’re all expensive. We must work carefully with the insurance companies and work through precertifications with the insurance companies to ensure that we have the indication right for the patient. At times, we must submit the actual data, and say, “This guy has a germline BRCA2 mutation. Here’s the result. Here are his prior treatments. He’s already progressed on abiraterone. He’s an ideal candidate. He has metastatic castration-resistant prostate cancer [CRPC].” We send all that in and then work it through the precertification process. Absolutely, the reimbursement is a significant issue, and the co-pays can be problematic for patients as well. Sometimes, there are programs that can help. It depends on the individual patient, their financial resources, their insurance resources, and at times, how hard we work the system too. There are a lot of factors that go into choosing the therapy beyond simple indication.

Matthew Fowler: Given all the options now for men with metastatic CRPC, what’s your preferred sequencing strategy?

Oliver Sartor, MD: I’m using hormones first—abiraterone, enzalutamide, maybe darolutamide or apalutamide if they’re not metastatic. I’m trying to get in the novel hormones first because we have an accumulation of data that earlier use of these novel hormones results in better survival advantages. In fact, we have lots of new data that demonstrate that in the castration-sensitive space, if you’re treating with these novel hormones, you do have an amazing effect on overall survival. I try to get my novel hormones as early as I can.

After you fail novel hormones, it gets to be a bit of a Wild West out there because there are many options available. At that point, I’m looking at those genomics and precision therapies that might be available. I’m looking for things like the mismatch repair. That’s where olaparib would come in, not rucaparib because that’s post-taxane. I’ve got olaparib and then pembrolizumab that are for specific patients based on the NGS [next-generation sequencing], the germline testing.

Then I’ve got taxanes—radium and sipuleucel-T—that I might throw in. One of my most common choices is the taxane docetaxel. By the way, I tend to like the 50 mg/m2 every 2 weeks, which isn’t FDA approved. However, there’s a beautiful trial coming out of Finland and headed by a good investigator who demonstrated that the 50 mg/m2 docetaxel, probably a little better tolerated and maybe a little more effective than the 75 mg/m2 every 3 weeks; there’s a bit of an artistic element there. Then we also have the clinical trials to consider. Those are important as well.

Matthew Fowler: Looking ahead, what other exciting advances are being made in metastatic CRPC?

Oliver Sartor, MD: I mentioned the Lutetium-177 PSMA [prostate-specific membrane antigen]. That’s the next FDA approval; it’s pretty clear. There are a series of combination trials using the PARP inhibitors, including 1 I haven’t mentioned called talazoparib, to be put together in combination with the novel hormones, either abiraterone or enzalutamide. There’s a pretty good rationale for thinking that the biology of the tumor may be particularly susceptible to combining the PARP inhibitors and a novel hormone. Those combination trials with the abiraterone-enzalutamide and a PARP inhibitor combo are ongoing. They haven’t been read out, but we’re watching those with interest.

There are interesting studies that are beginning to combine the PARP inhibitors in combination with a Lutetium-177 PSMA that’s interesting. Then there are combinations with pembrolizumab and enzalutamide. There are data to support that. There are newer compounds, like the VERU-111, out there. We have some Arvinas compounds looking a little interesting in some molecularly defined subsets. A variety of new things are happening. Probably the most predictable of the ones that I can see moving up with the greatest clarity are the Lutetium-177 PSMA. There are 2 agents that are using Lutetium-177 PSMA. One is from Novartis, that’s the Lutetium-177-PSMA-617, and the second is called PNT2002, also using Lutetium. Both are moving into that post–abiraterone-enzalutamide space with no prior chemotherapy. There are also up-front trials with Lutetium-177 PSMA, as well taking the castration-sensitive space. I’m pretty sure the Lutetium-177 PSMAs are going to move up; we need the trial data to prove that.

Matthew Fowler: Lastly, what clinical pearls do you have to share with colleagues who may not see patients with prostate cancer every day?

Oliver Sartor, MD: There are several things that I’d like to emphasize. No. 1, prostate cancer isn’t breast cancer. It turns out that a lot of these individuals aren’t able to tolerate quite as much chemotherapy as some of the patients with breast cancer. They’re often patients a little older; they’re castrated. There are 4 things that you need to be very open to: 1) the idea of precision medicine; 2) the idea of the novel hormones and using them earlier when you can; 3) the possibility of taxanes, when it’s appropriate to do so; 4) the possibility of clinical trials. There’s a big evolution going on. If you don’t have a particular clinical trial, then be cognizant of a center nearby that might be able to offer a good clinical trial is something to think about as well.

Matthew Fowler: Thank you so much for your time, Dr Sartor. Thank you all for watching this CancerNetwork® OncView™ program from MJH Life Sciences™. We hope you found this to be valuable to your clinical practice.

Transcript edited for clarity.