Alpha Emitters May Move Radiopharmaceuticals Forward in Prostate Cancer

At the 16th Annual Interdisciplinary Prostate Cancer Congress^® and Other Genitourinary Malignancies, Scott T. Tagawa, MD, MS, FACP, spoke with CancerNetwork^® about moving the needle forward for radiopharmaceuticals in prostate cancer care by improving upon existing agents and forming new constructs.

Tagawa, a professor of medicine and urology, and medical director of the Genitourinary Oncology Research Program at Weill Cornell Medicine, discussed how alpha emitters, including radium-223, were potentially more advantageous as treatment than beta emitters following prostate-specific membrane antigen (PSMA)-PET scans.

Tagawa also detailed the advancement of additional cell-surface targets in oncology, including chimeric antigen receptor (CAR) T cells and bi-specifics, and how radionuclides can factor into these types of therapy.

Transcript:

Taking our existing drugs and having them work better, and then new constructs [will push the needle forward].

In terms of taking what we have or what we think is coming, we can do better in terms of patient selection, and we can do better in terms of determination of the right dose and schedule. And then [for] combinations, I suspect that combinations are going to be better than single agents with the existing agents. Those are, in part, happening already, but additional work can be done. In terms of more novel agents, I would say we can take the same validated targets. For PSMA, let’s validate it diagnostically with PSMA-PET and therapeutically with the survival benefit of 177Lu-PSMA-617. And [we should] just change the beta [emitter] for an alpha [emitter]. Alphas that we already have approved, like radium-223, are much more potent. There’s room for them even against the same target sequentially or head-to-head because of the increased potency, there may be some advantages to that. Switching out the beta for an alpha is one way to move forward in terms of more novelty.

And then beyond that are additional targets. Across oncology, we are looking at a number of different cell-surface targets. Antibody drug conjugates are probably the predominantly approved option out there. We can use CAR T cells or bi-specifics in terms of using immune effectors. But [we also have] radionuclides, so anything that’s out there, at least in theory, should be a good target for a radionuclide whether it’s a beta emitter or an alpha emitter. We’re just at the tip of the iceberg. Even though we’ve had lutetium dotatate for a while in a rarer disease population, it has now exploded and taken over all the world’s supply, unfortunately, of 177Lu-PSMA-617 because prostate cancer is more common. Now, I see out there a number of different companies with way bigger numbers than we saw before that are looking to develop these compounds. These don’t necessarily have to replace antibody drug conjugates; there’s even the possibility of combinations. But as long as the target is validated, then I can see it in either combination or sequential use.