Prostate Cancer Nexus
Transcript: Advances in prostate cancer at ESMO 2025
Alicia Morgans, MD, MPH
Interview recorded October 2025. All transcripts are created from interview footage and directly reflect the content of the interview at the time. The content is that of the speaker and is not adjusted by Medthority.
- There have been so many highlights of ESMO 2025. I think that my favorite presentations have been the PSMAddition trial, which was looking at the use of Lutetium-177 PSMA-617 in combination with ADT and AR pathway inhibitor in patients with metastatic hormone-sensitive prostate cancer. And this combination demonstrated a radiographic progression-free survival benefit when compared to ADT and ARPI alone, which was I think very exciting to see this use of a radiopharmaceutical in the metastatic hormone-sensitive setting. Definitely more information to come to see how... And if we will ultimately integrate it here, but it was exciting to see. I think although the rPFS benefit was relatively small, the CAPItello-281 study also was really exciting.
Again, in a metastatic hormone-sensitive prostate cancer setting, this used... Patients who had tumors that were P10 deficient. And so really trying to capitalize on this molecular biomarker strategy and wondering if we can try to start targeting, in addition to what we do with patients with HRR mutations and PARP inhibitors, some of these mutations that make cancers uniquely susceptible. So again, there was a relatively small rPFS benefits, study was positive, so we will see where things go, and I think that it's, again, exciting that we might be able to harness these molecular characteristics. Otherwise the ENZARAD trial also, really exciting. A negative trial overall, looking at the addition of enzalutamide in the early stage of high-risk prostate cancer being treated with ADT and radiation. But for those patients who had clinical lymph nodes positive, the addition of enzalutamide did seem to improve their progression-free survival, which is also very, very exciting. And finally, EMBARK study metastatic... Or sorry, non-metastatic castrate-sensitive prostate cancer showing in overall survival benefit for the combination of leuprolide and enzalutamide versus leuprolide alone. Really, also, wonderfully beneficial to the patients and an advance for us.
So I know this was a long list, but an exciting meeting overall and I didn't even scratch the surface, many other things also included today. At ESMO this year, I do think the overall survival data from EMBARK for patients with non-metastatic CSPC will reinforce what we already have in guidelines and will ensure that hopefully, there's ongoing education around the use of enzalutamide in this setting as it does when used in combination with ADT, prolonged overall survival, which is absolutely new data for us. And enzalutamide, even if used alone, doesn't necessarily improve overall survival, but looks like it's at least equivalent, if not slightly better than leuprolide, at least numerically. So this is something already in guidelines that I think will be reinforced and will be continued to be in education. I do think that as was noted in the presentation, the ENZAMET study may be practice informing, possibly guideline informing, for patients who are unable to use abiraterone in this setting. It's possible if they have clinically lymph node positive disease receiving radiation and ADT for 24 months, maybe they'll be able to add in enzalutamide if, again, they can't tolerate abiraterone, which has been the standard of care for a long time based on STAMPEDE.
So these at least are practice informing, and EMBARK, I think is guideline reinforcing. I do think that the ongoing development of radiopharmaceuticals is something that we are all keenly aware of, and very, very excited about. And PSMAddition did move this Lutetium-177 PSMA-617 RLT into a metastatic hormone-sensitive setting, showing us that we can complete a registration trial there and we can show benefit at least in our PFS, and a trend perhaps to OS benefit. Though this also reinforced to us that when we have these early stage trials and we allow crossover, as was done in this study, it's going to be very hard to show a difference. But the RLTs are coming fast and furious, different targets, different radioactive ligands, and I think that we're all very excited to see that move forward. And then I can't emphasize enough the excitement that there is around understanding the molecular drivers of prostate cancer. And as I mentioned, CAPItello-281 before, this study may or may not end up being something that we utilize in clinical practice on a day-to-day basis, but it is laying the groundwork for further investigation of molecular changes that can be harnessed and used to treat our patients in a more personalized and directed way.
Developed by EPG Health. This content has been developed independently of the sponsor, Pfizer, which has had no editorial input into the content. EPG Health received funding from the sponsor to help provide healthcare professional members with access to the highest quality medical and scientific information, education and associated relevant content. This content is intended for healthcare professionals only.
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