Role of Precision Medicine in PSMA-Positive mCRPC


Evan Y. Yu, MD, shares insight on the rationale for precision medicine in patients with progressive PSMA-positive metastatic castration resistant prostate cancer (mCRPC) who have been previously treated with androgen axis inhibitor drugs and taxane.

Evan Y. Yu, MD: At this point, we do not actually have a standard of care yet for PSMA (prostate specific membrane antigen) positive metastatic castration-resistant prostate cancer. PSMA PET (positron emission tomography) imaging is really a newer modality in the United States. In other countries like Australia and Germany, they have been doing this sort of imaging for quite some time. There really has not yet been therapeutics developed targeted towards PSMA PET until recently. The current standard is that if you have a PSMA PET-positive patient, you have to default to your general treatment strategies that are FDA approved. Fortunately, with more clinical research, we have newer agents that are on a very close horizon that will be useful for patients that have progressive PSMA-positive metastatic castration-resistant prostate cancer.

PSMA-positive metastatic castration-resistant prostate cancer is a perfect opportunity to apply precision medicine to this field. We always think about precision medicine as being genotypic. You have a BRCA2 (Breast cancer gene 1) alteration, or you have a mismatch repair mutation that leads to microsatellite instability and hypermutation. Really, this is just a different type [of precision medicine. This is like phenotypic precision medicine where you can obtain an imaging modality—an image of protein that is highly expressed on prostate cancer—and be able to target new therapeutics directly towards that. The fact that PSMA PET imaging is a new modality that is going to be available for our use here in the United States and of course, is available in many other countries, is a real opportunity to develop therapeutics targeted towards that. Those therapeutics can be radioligand therapies, where you are bringing a radiopharmaceutical treatment directly to the cancer cells, decreasing toxicity and increasing efficacy that way. It can also be certain types of immunotherapies, antibody-drug conjugates, bispecific antibodies—there are just many, many opportunities. The other component to bring up is, it may be most ideal for patients with metastatic castration-resistant prostate cancer, and even for those who have received androgen axis inhibitor drugs like abiraterone or enzalutamide. There is data to say that PSMA expression seems to be higher in patients with metastatic castration-resistant prostate cancer, and it might even be higher in these patients that are further down the road as far as previous treatment.

This transcript has been edited for clarity.

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