Medicine Matters oncology

At ASCO GU, I'm presenting the results of the TheraP trial. This is a randomized phase II study of lutetium PSMA-617, which is a very novel, radio-labeled therapy for men with metastatic castration-resistant prostate cancer. This is a radioactive molecule which targets prostate-specific membrane antigen, or PSMA, overexpressed in metastatic disease.

And this is a phase II randomized trial conducted by the ANZUP Cancer Trials Group at 11 sites around Australia. We randomized 200 men to either lutetium PSMA-617 or cabazitaxel chemotherapy. And the results showed that lutetium had greater activity, fewer adverse events, and patient-reported outcomes favoring lutetium. So more specifically, the primary endpoint was a PSA decline of 50% or more. And that was seen in 66% of men randomized to lutetium PSMA compared to 37% of men with cabazitaxel.

That radiographic or PSA progression-free survival was delayed with lutetium PSMA with a hazard ratio of 0.63. At 12 months, 19% of men randomized to the lutetium arm had not progressed compared to 3% with cabazitaxel. Objective response rates using CT resist were 49% compared to 24%. And grade 3 to 4 adverse events, despite this greater efficacy, were lower with lutetium PSMA at 33% compared to 54%.

And importantly in this group of men, we looked at a lot of patient-reported outcomes. And the overall quality of life with the global health schools was similar. But we saw significant differences favoring lutetium PSMA for a variety of symptom endpoints, such as fatigue, diarrhea, hair loss, sore hands or feet, and urinary symptoms. So the conclusion of this study is that lutetium PSMA-617 is a new class of effective therapy for men with metastatic prostate cancer.

So the next step is that there is a phase III randomized controlled study being conducted by Novartis and AAA. This is an over 800-patient study. And this has completed recruitment. And we're really awaiting the results. This will give us a survival rate out and will lead to FDA registration in the USA if it is a positive study.

In the meantime for men where this therapy is available, and it is available in some parts of the world, the TheraP trial, although only phase II, really provides compelling evidence that it is a potential alternative to cabazitaxel. We did not yet reach enough deaths in this phase II study to actually perform a survival analysis. So at the time of follow-up, there were only 90 deaths in total. And that was insufficient. So we will perform a further analysis of the TheraP study next year to look at that survival endpoint.