Baseline characteristics of patients with PSMA-PET–positive and –negative disease with high-risk BCR after radical RP

Prof Boris Hadaschik - University of Duisburg-Essen, Essen, Germany

Here this year at ASCO GU I presented a poster on the baseline characteristics of the phase III PRIMORDIUM study. The PRIMORDIUM study is an ongoing global phase III study where we test whether the addition of apalutamide to six months of ADT in the context of men with high-risk biochemical recurrence after radical prostatectomy, whether that improves a novel primary endpoint which is PSMA-PET-based metastasis free survival. So I’m a urologist, I’ve been heavily involved with PET imaging over the last decade so I’m very happy that this study is one of the first to really implement PET, not only as a baseline test in biochemical recurrence but also through follow-up and as a primary endpoint which certainly then is validated with secondary endpoints such as conventional MFS and OS and these things.

Here we presented the baseline characteristics because the study has a little bit slow accrual and now we can make the study a little bit more pragmatic. So in the initial design we only included patients with PSMA-PET positive disease in the pelvis but we noticed, now analysing the first 200 patients, that half of the patients had negative PSMA-PET at baseline. So these patients were only eligible for the observational cohort but not the real trial cohort where we randomised apalutamide.

What we then compared are the clinical factors. So patients with negative PSMA-PET and positive PSMA-PET the only real difference was PSA values, so negative was 0.3, positive was 0.5, and the time since radical prostatectomy which was longer for the patients with positive signal. So it shows that the biology between the two groups is not that much different, it’s only an issue of time and waiting a little bit longer until the PSA goes higher. But the proportion of men with high-risk disease in the prostatectomy and the proportion of men with short PSA doubling times was similar between the two groups.

So now there is amendment 3 of the PRIMORDIUM study where we can really treat and include all patients. Because in clinical practice we don’t want to delay salvage radiotherapy until we see something but we want to really with curative intent treat the patient at the time of biochemical recurrence. This can now be done in the PRIMORDIUM study and I’m also happy, having seen the FORMULA-509 presentation at this congress and last year, that I believe that six months of intensified treatment are really a very promising way to go forward because we all know that even after six months it takes some time for quality of life to come back.

What is the clinical impact of these results and what is next for the study?

As I told you, the PRIMORDIUM study is still ongoing. So amendment 3 is really an important part now for our study because it will help us to push the study a little bit quicker over the finishing line. Because I firmly believe that an intensified treatment in the context of high risk biochemical recurrence in combination with good radiotherapy really can make a difference and increase the proportion of men that we are curing from the disease.

So PRIMORDIUM really is the first phase III study in this context, to really push apalutamide maybe over the finishing line. The ARASTEP study by Bayer is testing a similar hypothesis but with two years of ADT plus/minus darolutamide and a PET-based endpoint. So this is interesting and then we just can learn about what to do after prostatectomy has not cured the patient. So this has real clinical implication and right now if you look at the EMBARK study which has a similar disease spectrum but later on, EMBARK included men after salvage radiotherapy, so EMBARK is a palliative concept but with excellent outcome data.

So here with PRIMORDIUM we really tried to increase the fraction of men that we can cure. So it’s an important study and I’m very thankful for all the investigators helping us and physicians sending us patients to be included. Hopefully we’ll be here at some point in the future to then really talk about results. This is just descriptive characteristics.