New Precision Medicine Approaches in Advanced Prostate Cancer

EP. 6A: After VISION: Phenotypic Theranostics in the Future of Precision Medicine

In the final interview of the series, Oliver Sartor, MD, medical director at Tulane Cancer Center in New Orleans, Louisiana, discusses the aftermath of the VISION trial, new research examining 177Lu-PSMA-617 in less heavily pretreated patients and in combination therapies, forthcoming advances in PSMA imaging, novel biomarkers, the horizon for prostate cancer therapy and research, and the future role of theranostics in precision medicine.

So the VISION trial was a very typical advanced, advanced patient with chemotherapy exposure. [W]e're hopeful that these earlier stage trials with PSMA-617 lutetium are going to result in more regulatory approvals for less heavily pretreated patients than were present in VISION.

PSMA lutetium-177 is being evaluated in combination with things like PSMA actinium-225. It's being looked at in combination with DNA repair inhibitors such as the PARP inhibitor olaparib. It's being looked at in combination with the PD-1 inhibitors like pembrolizumab. It’s being evaluated in combination with stereotactic body radiotherapy. So as we move forward, combination therapies are important.

Different ways to image PSMA may also be important. There [are] also image-based biomarkers related to the use of immunotherapy. And being able to image things like PD-L1 is also quite important, potentially. So as we go forward, I'm seeing a whole series of newer PET markers being evaluated and utility, perhaps growing out of even combinations.

I think the short-term horizon in prostate cancer is going to revolve about moving these novel radiopharmaceuticals closer to the front of therapy. In addition, we're going to see the rise of these combination therapies initially in phase 1, moving on to phase 2. And then I think we're going to evolve a whole series of novel biomarkers, and these are going to require additional testing, of course, but the field of biomarkers is alive and well and evolving so, so rapidly right now.

When we talk about precision medicine, I think most of what we've become accustomed to—but not all—is related to the genomic alterations that occur in the context of cancer. But phenotypic alterations such as PSMA expression—this is not going to be something you can detect with a gene rearrangement. It's really about protein expression. I think this area also has a bright future. I envision many, many more theranostics going forward.