Emerging Therapies for Advanced Prostate Cancer

Daniel J. George, MD: We're running short on time. We have about 10 minutes left, and I know Eleni has been really quiet. It's really great. I appreciate it, Eleni. I know this is a topic here that you really want to talk about. You brought up the Jean Hoffman-Censits, MD, abstract at ASCO . When we think about the promising emerging therapies for prostate cancer for the future, lead us through where you think 177Lutetium-PSMA-617 is.

Eleni Efstathiou, MD, PhD: Honestly, I like the comment, “I appreciate that you’ve been quiet.” I think it created the segue by Ben, who said that he considers radium-223 more precise than not, versus how Chuck presented it. I think the next step is exactly that. It's the treatment that would be more precise and to the point with a radiopharmaceutical. It's a great segue.

While we're waiting for phase 3 trial data that are probably going to come out at ESMO [the European Society for Medical Oncology annual meeting] or at least this year, hopefully, I think that this first look at the phase 2 study that was designed very elegantly by Hoffman, et al, gave us a first view of those men who are further along in the disease course gave us a promise of what may happen. They actually looked at a randomized schema of men who had progressed through other approved agents but had undergone PSMA PET and an FDG PET. That's really important.

I don't know how feasible that will be in the future in this country, but they did both, and they looked at accruing men who had mCRPC and had concordance of both of the PSMA PET and the FDG PET findings. If there was discordance—let's say there was an FDG PET positive but negative on PSMA PET for that lesion—they didn’t go on trial. It was a more homogeneous population. I love that. Then, they randomized. Let's go for the 177Lutetium-PSMA-617 versus the cabazitaxel. The primary end point was what you would expect from a phase 2 study. They’re looking at the PSA value.

They're looking at rPFS. These end points were well-met. The secondary was OS. I think their data were positive for that, too, even though they weren’t mature. It was a first glance at their data set, but the important part was a staggering response by PSA criteria to favor the use of 177Lutetium-PSMA-617 versus cabazitaxel, which looked like it was underperforming.

To Chuck's point, it’s because that is not as precise a treatment, so it might be a more all-inclusive disease approach to life. That's why I like the study a lot, and it speaks to the fact that if you pay attention to the details, you might get to your point quicker.

Daniel J. George, MD: Fantastic. Any thoughts on that, Chuck or Tanya?

Charles Ryan, MD: I think it's a key finding that the 177Lutetium-PSMA-617 is potentially hitting both of those themes. It's a targeted and precision therapy. I wonder if patients are going to be more likely to be able to take 177Lutetium-PSMA-617 than chemotherapy or would be willing to take it. I do have to say, I find cabazitaxel to be a relatively well-tolerated therapy, with regard to chemotherapy.

Daniel J. George, MD: I don't necessarily see us replacing one drug with another, but I do see that there will be patients that might be more responsive to one strategy or another. I think this is where some of our biomarkers would be helpful. Obviously, the VISION study is what we need to see. We don't have those data yet. We'll do another program when that comes on and be able to discuss that, and it’ll be interesting to see where the imaging falls for this, because we talked about PSMA PET imaging as a way of looking for metastatic burden.

Now, we'd be doing it differently. We'd be looking at it in terms of a biomarker for selection. Tanya, does that change how you think about using PSMA PET, if you're thinking about it from a biologic profiling rather than a tumor burden perspective?

Tanya Dorff, MD: It’s very exciting to view it as a theranostic where you can do the diagnostic testing and show the phenotype. This is a cancer that’s expressing the target, as opposed to all these genomic strategies where we're looking at what the DNA says. There's something very appealing about that. I'm seeing the target in this patient, and I'm going to apply the treatment. I do worry whether the imaging component is going to be lost in the application of that agent. I think a lot of attention, as Eleni pointed out, to concordance, intensity of uptake, and who does well might be important in maximizing the impact of this agent, which we're all very excited to have added to our therapeutic toolbox.

Engaging its relative merit for an individual patient, I think we'll need to refine the biomarker. If anything, that makes me more enthusiastic. We always want to choose the best treatment for a patient. We always want to have a biomarker that helps us do that in a more scientific way. We’re scientists at heart, and data junkies, too.

Daniel J. George, MD: Absolutely. I want to thank you all. This has been an incredibly informative and rich discussion. I really appreciate everyone’s input and insights. Before we conclude, I thought I'd give each of you a chance to summarize what you think are the most important takeaways from this session today. Chuck, do you want to start us off?

Charles Ryan, MD: Obviously, we're seeing a lot of incremental progress on a lot of different fronts. It's really encouraging. We're, for the first time in my career as a medical oncologist focusing on castration-resistant prostate cancer, we're talking about people who are living so long that prostate cancer is fading a bit as a cause of death for these patients. When you talk about big shifts in our field, they don't happen overnight. But when you think about what we talked about on these types of meetings 5 years ago, it's a very different situation. That's really encouraging. We have a number of key studies underway.

We have our first genomically guided targeted therapy that just got approved. It's a very exciting time. It's a challenging time because while we get excited about these new agents and their ability to treat patients, we also get humbled by the fact that they don't always work in everyone. Even the people in whom they do have efficacy, it's not as long as we'd like. I am inspired to continue to study the biology of this disease, its evolution in patients over time, and how that can be applied to the population. I'm always delighted to work with you, my colleagues, on these projects.

Daniel J. George, MD: Awesome. Tanya, do you have any closing thoughts?

Tanya Dorff, MD: To bring it back to the patient who’s at the center of all of this, it's so gratifying and important that these studies look at patient-reported outcomes and take into account quality of life. That has to be part of our discussion with patients when we're talking about the benefits and experience. There's also that third component of financial toxicity and concern, so it becomes more complex in our jobs to try to guide patients through.

It is important for us to look at all those aspects. There are so many great new treatments. Patients are living longer. They're largely living better, too. It's increasingly our job to help patients navigate and translate what these studies show us into what they will experience, what their day-to-day life will be like, and what it means for their lives and their PSA levels not just now, but 5 and 10 years from now. Those are challenges for us, but I know we can rise to the occasion.

Daniel J. George, MD: Fantastic. Eleni, any thoughts?

Eleni Efstathiou, MD, PhD: I don't want to be repetitive. I want to add one more point that I believe comes across from all of us. We all feel privileged and have had the opportunity to try a lot of these drugs firsthand. In a way, we're also privileged in our practices being mainly academic settings. It is also our responsibility to reach out to the community and offer a hand of trying to get everyone on board, because it will mean nothing unless it gets to every single patient out there. I think that's what we all agree on.

Daniel J. George, MD: Fantastic. Finally, Ben, from the urology perspective.

Benjamin H. Lowentritt, MD, FACS: I appreciate Eleni’s comments there, because I think the mission for us is clear. Whether as urologists, we're deciding to treat these patients or not, we have to be dedicated to finding them and understanding that these options are available for patients. They're better when we identify them as early as possible and get them on the right road.

Also, I'm very fortunate that I get to dedicate my time and efforts to this, but a big part of what I'm trying to do is help my partners make sure that we're finding these patients and offering all of the therapies that we can, because it doesn't do anyone any good if the patients aren't getting to the therapy. I really appreciate the discussion. It's been very enjoyable, and I look forward to future talks.

Daniel J. George, MD: Fantastic. Thank you to you all again, and to our viewing audience. We hope you found this OncLive Peer Exchange® discussion to be useful and informative, and look forward to having you join us again in the future. Thank you.

Transcript Edited for Clarity