We presented data from the PSMAddition trial that’s a phase III study involving lutetium-177 PSMA-617, otherwise known as Pluvicto. The trial was for those folks who have metastatic castration sensitive prostate cancer which, per Working Group 4, we’re now calling APMS, or androgen pathway modulator sensitive. These patients had to have metastatic disease that was positive on a PSMA-PET scan and they were randomised to either ADT and an ARPI alone or with up to six cycles of Pluvicto for up to 36 weeks of treatment. Then after those 36 weeks everybody was just on the ADT and ARPI.

What were the results of this study?

The primary endpoint of the study was radiographic progression free survival, per Prostate Cancer Working Group 3. Secondarily we looked at overall survival, the patient-reported outcomes for quality of life and pain, and also time to first SSE. The study was a positive study for its primary endpoint and that had been reported at ESMO and the hazard ratio of that was 0.72 in favour of the triple therapy with lutetium.

At that meeting also the top-line results for the quality of life data were presented and we presented at this meeting the detailed longitudinal results of the quality of life, the pain and also the SSE data.

What is the clinical significance of these results?

The clinical significance of the top-line data from the primary endpoint is that you are exerting superior disease control if you have triplet therapy with the Pluvicto. But really what we were looking at in terms of the significance of the results presented at this meeting is a really detailed look, now that you know that the disease is controlled in a superior manner with all three drugs, what is the experience of actually being a patient in terms of functioning and in terms of the quality of life. This was the first look at the details of that quality of life data.

At ESMO Dr Tagawa presented time to a decline, or time to worsening in quality of life and time to worsening of pain. Those data, a lot of people who saw them walked away with a misapprehension of those data. Because the Kaplan-Meier curves reflect a time-based event, meaning that if you have a decline in quality of life at any point, that counts as an event, the patient is censored, and even if the patient’s quality of life improves over the course of treatment you can’t reflect that in a time to event endpoint.

So what we presented here was the actual quality of life at a whole series of pre-specified timepoints throughout treatment of both arms. So you could now see the dynamic course of quality of life as patients on each arm either received doublet therapy continuously or, on the experimental arm, triplet therapy with Pluvicto first and then doublet therapy from that point on.

So the results actually were quite interesting. So you saw that there was a divergence in quality of life between the two arms during those 36 weeks in which the experimental arm was getting triplet therapy with Pluvicto. But then those datapoints reconverge when they’re back on doublet therapy, the two arms look very similar. And the time period that I’m talking about is when we have really good data for and that’s from the period of randomisation to 108 weeks. After that the data really falls off, we need to have more time in order to see what happens after those 25 months. But a lot of people walked away from ESMO thinking, ‘Oh, the quality of life is more poor if you receive the Pluvicto.’ That is not the case. It’s only the time period during the treatment of the 36 weeks, and this is by virtue of the fact PRO that you saw some divergence during that period in which one arm was getting three drugs and the other arm was getting two drugs, but after those 36 weeks the quality of life is quite similar.

We used another tool to assess quality of life in addition to the FACT-P and that was the EQ-5D-5L utility score. That quality of life was exactly the same between the two arms throughout the duration of the trial, at least through 108 weeks for which we have good data. 

Then finally we found that the pain control was the same between the two arms over the course of the treatment follow-up period and then it was the same for time to first SSE, both including death and excluding death as an endpoint.

So although many people walked away from that ESMO presentation thinking that there was a difference between the two arms and quality of life, that’s because they were looking at data that was basically a time-based event as opposed to a true quality of life-based event. Where you look at the quality of life data now, in detail, at the actual measured, quantitative quality of life at each timepoint, you can see details that really these two regimens are quite similar in terms of quality of life and the only difference in the FACT-P is during the period of the triplet therapy.

Is there anything else you would like to add?

The third piece of this study that we’re all waiting for is more mature survival data. So we have now a trial that’s positive for its primary endpoint, rPFS. We have data on quality of life during that period that shows that the two arms are relatively similar except for one assay in the early part of the treatment course, what we really need to see now is how overall survival plays out. Because you want, when you’re assessing the data from any trial, not to look at any single endpoint, you want to look at the totality of the data and overall survival is the least mature of the endpoints that we have right now.

The preliminary look looked good, as was presented at ESMO, but we need more events to really feel confident in that.