Drug Boosts PSMA-PET Signal for Prostate Cancer in Small Study

A short course of darolutamide (Nubeqa) enhanced the imaging signal of prostate-specific membrane antigen (PSMA)-PET in a subset of patients with high-risk localized prostate cancer, according to findings from the phase II Daro-PET study presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium.

In this exclusive MedPage Today video, Jose Mauricio Mota, MD, PhD, of the University of São Paulo Institute of Cancer, describes how brief androgen receptor inhibition may improve imaging interpretation and outlines next steps for translational analysis.

Following is a transcript of his remarks:

Daro-PET is a trial including patients with high-risk localized prostate cancer. Patients underwent a PSMA-PET scan and then received 7 days of darolutamide. And after that short-course treatment, they get another PSMA-PET scan.

The primary endpoint was to compare the PSMA-PET 2 with the PSMA-PET 1 and see if patients would increase the SUVmax [maximum standardized uptake value]. So, if a patient increased the SUVmax in 20% or more, we would declare that the patient achieved the primary endpoint.

Secondary endpoints included tumor volume measured by the PSMA-PET scan and also other PSMA-PET scan measures. Also, we evaluated the changes in the management of these patients and also the feasibility and toxicities from this short-course treatment.

The trial achieved the pre-established primary endpoint. It was a positive trial. Three patients out of 16 patients included achieved this effect. They had an increase in the SUVmax of 20% or more, so it was 18% of the whole population. And when we evaluated only the per-protocol population, which was the patients who effectively received the treatment in the pre-established doses of the Gallium-68 radiotracer, we had three out of 14 patients achieving the primary endpoint.

When we looked at other PSMA-PET measures, we found out that 50% of the patients had an increase in the tumor volume measured by the PSMA-PET 2 compared with the PSMA-PET 1. No patients had change in the management, and the treatment was considered feasible and no toxicities were reported.

Now we’re planning to take a deeper look into the translational part of this study. We are now conducting IHC, immunohistochemistry, testing to see if the increase in the SUVmax would correlate with an increase in the PSMA expression using the immunohistochemistry assays. And also we are planning to run RNA sequencing molecular tests to see if there was any sort of a difference in terms of gene expression of the PSMA gene. Also, we are planning to run methylome tests to see if there’s any change in the epigenetics of these patients.