Read the Full Video Transcript

Silke Gillessen: Our trial organization is called SAKK and is a bit awkward challenges and opportunities coming from a small country. These are my conflicts of interest, very long. And for our foreign guests, because a lot of people don't know where Switzerland exactly is, especially in the States, I think there's a confusion with Sweden. That's us. And it's very, very small. 40,000 square kilometers, 26 counties, very complicated. Eight million inhabitants, four languages.

This is a country that I guess a lot of you have never heard of. This is our population. That's also a bit our problem. We have a rather homogeneous population, all men look like that. And we don't have diversity in our country plus or minus. We have a very long life expectancy. We normally in the world number two mostly. We have also a high cancer incidence population. And one of the problems that is very different I think from England, is we have unwillingness of patients to travel for care to larger centers. And also because five minutes for them on the train is already a lot. And Laura is smiling, it's like that.

And we have access also to new drugs rather easy. This is, I mean, very nice for our population but obviously also makes it a bit more difficult to make someone enthusiastic about going into a clinical trial. Because we have enfortumab since months already available, we just ask the insurance. We have even Pembro for MSI-High, we just ask the insurance. There is a paper and we mostly get it. It's a bit different from other countries.

What was our clinical research group? It was actually founded in 1965. Because most of our old oncologists were in the states. Our beginners of oncology were all coming from the NCI. They knew the NCI and they wanted to do something kind of similar in Switzerland but was obviously at that time not so easy. But they tried for the clinical part to found this SAKK. And SAKK for GU was a time very, very active with Studer who probably some of you still know. Studer was there and he was doing a lot of trials. But then when he decided to go more European in EOTC then the GU group died off or slept a bit, let's put it that way.

And then I came back from Boston and I started to do GU, and I revived together with George Tolmond the GU group about 2019. George helped me a lot in that time. But we had to start small, so we had these small non randomized phase two trials mostly in metastatic castration-resistant disease. But we always had a translational part as well. That was quite good. And then here I think that that is also a very nice consortium where I just wanted to tell you that we also part of that via the SAKK, that Karim Fizazi and Bertrand Tombal kind of grounded or whatever. It is just like an artificial group, the PEACE consortium, where you as academic group can, if you have more than three groups interested, generate new trials.

And I think that's quite a nice concept. But you have to find your own money what is always the problem, as you know. Also in the SAKK we had some money problems, so that's a bit surprising in Switzerland. But it happened. There were some things that didn't work out as planned. And here is our new organic ground that we made, so people realize that maybe on the board shouldn't be only doctors because they don't know so much about finances. Now we have also financial people and some also politicians in, because what was missing is that political pressure to do clinical trials. And the GU group is one of the project groups in the SAKK. So there's hema-oncology and oncology. And I just show you what we did, these were all Metformin. I already did Metformin before we went into STAMPEDE but in the MC or PC state and we had a little bit of activity, very small, but we did a lot of again, translational research. I found that very interesting.

And then we had some other trials, a maintenance trial with Orteronel, you know probably that this then had to be stopped because the drug wasn't pursued. We have also a quite active group members from the radiotherapy, and they did a quite large phase three trial for salvage radiotherapy, a different doses. And then I think the smartest decision we ever made is to collaborate with STAMPEDE. I'm really happy we did that, because I know that you also approached EOTC at some time point and they said no, we at Swiss said, "Oh yes please, please." And it was really I think probably one of the most intelligent things we did. And then I guess one of our interesting trials I think is a phase three trial, Denosumab monthly versus three monthly. And I come to that later. When you see the last five years for the publications, you've seen red really most STAMPEDE.

So thanks to STAMPEDE, we have been on the author list, on a lot of trials. Again, when you come from a smaller country and I know Italy is very big. But if you come from a smaller country, it probably really makes a lot of sense to go for phase three trials together with other groups. And then you see in green we have some bladder cancers specifically because also from the Ur-Stude era. There are still a lot of people interested in non-muscle invasive bladder cancer, and that's nice. But that was with the help of German centers. The same thing as we said the radiotherapy, we had a lot of help from the German centers and then we have a very enthusiastic radiotherapist who wanted to do a trial in seminoma and he wanted to do it on his own first, stage two A/B. And I said, "Alexandro, I think we have to go to the Germans to make them help us." And we have now published the first paper. So that's quite nice.

With a combination a little bit like raw powder does involve lymph node radiation plus a little bit of carbo but is clearly less toxic. This is our ongoing studies that is already the second study in seminoma stage two A and B, because we saw it wasn't enough what we did for the stage B. So we now have two different treatments. We have then perioperative treatment in bladder cancer, very similar to what has been shown with also adding BCG. We have that affinity to BCG. But it was a bit problematic with really having the BCGs, not something, don't know what is in other countries, but in Switzerland sometimes there is a shortage of it. And then we have the phase one studies that we have also together with the phase one group of the SAKK. And in general we have a little bit focused because we are small on MCRPC including translational research and you saw Andrea Alimonti because we have a lot of these guys who have really a fantastic background for translational research. We can do that easily.

Salvage radiotherapy, we have the second trial running and BCG is I think, still from all a bit our interest for bladder cancer and then the seminoma. And I think this is quite interesting at least for us. We try to find a new founding opportunity and that was in collaboration with Santesuisse. That is a society of private insurances, because in Switzerland we don't have a national health system. We have private insurances, a bit like in the States I guess. And we tried to make clear to them that they should fund our study because that study is the prevention of Symptomatic Skeletal Events with Denosumab. And as you know, usually it would be given every four weeks. And we wanted to give it only three weeks because theoretically that should be enough.

It's a non-inferiority trial. So for us in Switzerland, obviously something that is quite a big endeavor. And you see here we decided to have patients with MCRPC but also with breast cancer. And arm A is just standard of care every four weeks and arm B is loading those first and then every three months. And the primary objective is obviously to see that it's non-inferior if you give less. And so this was our slide that we show to the insurances. The cost per patient per year in routine clinics in red. If they fund our study with all what the study costs but you have to obviously give much less, Denosumab because in Switzerland is not very cheap. That would be the cost per patient per year when they would agree with our study. And in green you see what would happen if we are successful showing that we are non-inferior. And we were quite successful with that.

So at least in the beginning they said okay yeah we are going to pay for it. The financing of the trial is cost neutral for them. Potential cost reduction if the trial will show non-inferiority. We hope obviously that less toxicity is associated with reduced secondary costs as well for the insurances. And then we said it would give them a good PR if they have a track record for supporting modern patient friendly trials. And as I said, it did work in this. He's laughing, but I mean it's quite true. It did work. They financed, now they have said okay now they want to stop because they are. But I think we are going to finish the trial hopefully next year. And then I think someone talked about it this morning, but I think it's also important and because also Andrea and like Johann, am also involved in EOTC.

I think we should also say, okay there is important clinical questions in rare situations of a rare cancer even that we can't only really answer with the global collaboration, like the TIGER study. I was very much involved because I was at that time the responsible for the EOTC GU group, and Tom Powles who we all know and love was like, first wanted to do the trial with EBMT and then they weren't really interested. And then I could just get it into EOTC in time to the board that we could start it from the European side. And you have seen the slides, I think it's a really important question, conventional versus high dose in the first salvage. And just to let you know, so it wasn't that easy. Alliance had the NCI funding for Europe. Europe we had Movember funding, so Movember really big thank you to Movember.

But just to let you know it wasn't that easy. The collaboration with Alliance from the European side, Andrea, you may also remember. I think I spent hours on the phone. It was quite difficult at that time. These international collaborations sound really good but legally and administratively it can be quite difficult. I think we should always think about that. How it can be improved? I think in summary, academic groups are really important for development of new trial designs as Noel has shown the norms. Then also there is ideas of near equivalence instead of making non-inferiority trials that comes from Ian Tanox's group. And also it's really important to answer important clinical questions that are of no interest for pharmaceutical companies. Like the deescalation trials, that trial that I showed you right now or drugs like our trial with Metformin.

I think there's just no interest or repurposing of drugs. This is probably something we have to do. And then the main question I guess we can then discuss these. How can we make international collaboration of academic groups also easier? And I think can we do them with less bureaucracy? Especially with the Metformin, right? I mean Metformin is well known said, I don't know, 50 years. But still we have to do all the safety reporting as it will be a new phase one whatever bispecific antibody. Why is that? I mean that's a bit weird and we all know all the paperwork we did before. Now it's even worse with, to be honest with all the digital stuff that comes in. And I think we would need an advocacy group from all of us saying, "Hey guys, if we do a dose reduction trial, if I do then Denosumab only three months versus every month, it's not very live likely that it is more toxic."

So why do I need to really collect all that data? It doesn't make a lot of sense. But there I think globally we should work on that. And then that is what we try to do with STAMPEDE International. Can we perform the same protocol in different country's groups and just share the data? And I think this is something that maybe we should do more and more. Statisticians at least say there is no problem when we decide on it from the beginning. I tried to do it in a very small scale with an active diet. You can remember our trial with exercise and diet for patients with prostate cancer together with someone in Australia. Let's try if it's working. But that you have much more legal and administrative stuff and I think the problem is probably then the authorships can be solved. I guess this is a bit what I think we should do as a community. Thank you very much.