2019 GU Cancer Symposium Wrap: Targeting Anti-PSMA

The 2019 Genitourinary (GU) Cancers Symposium wrapped up with more than 4400 attendees gathered for talks, posters, and discussions centered on the management of GU malignancies. A plethora of new trial and study results were presented during the three-day scientific and educational meeting, with many focused on the androgen signaling pathway or optimizing existing chemotherapy use. While these advances should be lauded for their continued progress, developments in new targets and drug action modalities could make immense progress for many patients.

The last two years have seen a groundswell of interest in what might be a new leg of treatment in mCRPC: anti-prostate-specific membrane antigen (PSMA). The non-overlapping mechanism of action with existing anti-hormonal and chemotherapeutic regiments potential for patient benefit even in those who have been heavily pretreated or have very large volume of disease. Researchers from around the world, including at the Peter MacCallum Cancer Centre in Australia, are quickly turning that potential into reality through updated analyses of very impressive early results seen in this report.

Their poster walk gathered keen interest and discussion
People were especially drawn to results of the PSMA PET/CT shown in their poster

A few extraordinary images aside, the prostate specific antigen (PSA) waterfall plots were noteworthy for the proportion of patients having greater than 80 percent PSA decline, indicating strong responses in even heavily pretreated patients.

One potential use of Epic Sciences’ Functional Cell Profiling is to better identify patients who might have the best PSA responses before undergoing therapy, potentially aiding the choice of whether to give anti-PSMA in the future, how many cycles to optimize benefit and side effects, etc. Previous iterations of anti-PSMA tech used cytotoxic chemotherapeutic payloads, which have been refined to radioactive lutetium-177 PSMA-617 (LuPSMA).

Epic Sciences developed an assay to characterize the PSMA protein expression on circulating tumor cells (CTCs), and utilized the assay to better understand the pharmacodynamic effects of an earlier anti-PSMA agent, recently published in JAMA Oncology:

While a small cohort, patients who had no PSMA positive CTCs after therapy initiation fared the best. The published report showed that the team was able to resolve single-cell PSMA expression heterogeneity in CTCs, which would potentially aid PSMA-specific radiographic imaging to better predict patient response.  The potential to apply this assay to aid our collective understanding of how exciting new treatment modalities like LuPSMA function on CTCs, and perhaps identify those that might have responses akin to the ones in the previous images.