Lessons Learned in the STAMPEDE Trial - Nicholas James
April 30, 2022
Professor Nicholas James, MBBS, FRCP, FRCR, Ph.D., Professor of Clinical Oncology at the Institute of Cancer Research at Royal Marsden Hospital, London
Phillip J. Koo, MD, FACS Division Chief of Diagnostic Imaging at the Banner MD Anderson Cancer Center in Arizona.
STAMPEDE Analysis of Abiraterone With or Without Enzalutamide Added to Androgen Deprivation Therapy Compared to ADT Alone In High-Risk Non-Metastatic Prostate Cancer Patients– Gerhardt Attard
STAMPEDE Trial Updates in Prostate Cancer - Silke Gillessen
Abiraterone Acetate plus Prednisolone for Hormone-Naïve Prostate Cancer: Long-Term Results from Metastatic (M1) Patients in the STAMPEDE Randomized Trial - Nicholas James
Quality of Life in the Treatment of mHSPC: The STAMPEDE Trial - Hannah Rush
Phillip Koo: We're back at the 13th International Uro-Oncology conference here in Brazil.
We have with us, Dr. Nick James, who is the Professor of Prostate and Bladder Cancer Research, at the Institute of Cancer Research at the Royal Marsden Hospital in London. He really needs no introduction, but we're very fortunate to have him with us today.
So, Dr. James, you're giving this lecture on lessons learned in STAMPEDE. STAMPEDE has been such an impactful trial in so many levels, that's been going on for decades.
Nick James: Yes.
Phillip Koo: Can you impart to us, some wisdom with regards to STAMPEDE, especially, for the Latin American countries, which are really ramping up their involvement in clinical trials?
Nick James: Yes. Thank you. So I think the first thing we've learned from STAMPEDE is lessons around how trials are set up and conducted. So one of the things we were very keen to do when we set it up, was to get involvement of as many UK centers as possible. Because we think, a lot of the time, trials are carry that in academic centers, and you get results that apply to a niche of patients that are managing the specialist centers, and not necessarily applicable to the broader population. So we set the inclusion criteria very broad, and we were very fortunate when we were setting it up, that the UK government had reviewed its approach to medical research, and decided that, research was a core functionality of the British National Health Service, the NHS, rather than a separate function for universities.
And so that meant that, the hospital, or NHS Trust, were financially incentivized to put patients in trials. The more patients you put in, the more money your hospital got. So it meant, when we were trying to set the trial up, the finance directors in the hospital, weren't saying, "Well, somebody's got to pay for this extra treatment.", because the government was deciding it was going to pay for it, unless we could leverage funding in from a pharmaceutical company, for example.
So that allowed us to, when we set the trial up to... In the first instance, we were studying drugs where we got pharmaceutical buy-in. So the first three drugs, we studied docetaxel, zoledronic acid, and celecoxib, the relevant pharma companies funded them. But more recently, we funded other things, like radiotherapy to the primary, being metastatic disease, or repurposing estrogen patches as an alternative way, doing androgen deprivation therapy, where we have no pharmaceutical support, but the government pays for it. And then, those two things have allowed us to get very broad based recruitment, which I think, is an important lesson. That means you get results that are applicable to everybody, rather than just a niche that goes into typical licensing trials.
Phillip Koo: I think that's great. And obviously, the governments have an incentive in this, especially with the way that the payer process works in the UK. And I imagine, a lot of Latin American countries could probably adopt something similar to this.
Nick James: Well, I think so. I think it's very important. The health care system has a direct vested interest in better outcomes for patients, using its technologies that are in use anyway. So the radiotherapy in metastatic disease is a very good example. It's an academic trial funded with support from UK charities in the UK government. And we ended up showing that, for a subset of the patients, about half of the metastatic patients who are radiating the primary, improves the survival. It was literally, instantly implemented as soon as the results came out. Because literally, every radiotherapy center in the country put patients in the trial, they were invested in the trial. They understood the results. They were happy to believe the results. So not only did we drive change in practice, but we drive the implementation at the same time, by recruiting from the centers that took part. Yeah. That everybody had a stake in the results.
Phillip Koo: I think that's so important, that transition to implementation. I think, you could scale it immediately, which is wonderful.
Nick James: Yeah.
Phillip Koo: So what are your top two, three, memories from STAMPEDE, now that it's been 20 years? Has it been?
Nick James: Coming up to 20 years now, since we first... It is 20 years since we sketched out the first design of it, actually. Well first, I do have to keep pinching myself as to how lucky I was that I got the chance to run this. Just everything lined up to make it happen.
By trialing multiple different things, we get lots of spinoff benefits. So for example, the docetaxel recruitment and the abiraterone recruitment overlapped. That allowed us to directly compare all sorts of things, like the quality of life between docetaxel randomized patients and abiraterone randomized patients. Nobody else has done a trial comparing those things. As we move now, to the situation where we are wanting to potentially combine docetaxel and abiraterone in it, if you like triple therapy, we can work out what the quality of life implications of that will be. And there are no other data that will allow you to do that. So that's one of the things that has been very impactful from it.
The other thing is, by having, as it is now, over 11,000 men randomized, and they're all consented for translational studies. So we've got germline DNA on 8,000, we've got baseline imaging on a similar number. We've got tissue biopsies on around 5,000. Within two of the arms, we've got serial circulating tumor DNA collections. So we've got a growing gold mine of translational research, that we're able to leverage off the back of it. And in the randomized setting, this is invaluable. Because we can see what the RNA expression profile was, and how it interacts with adding abiraterone or adding docetaxel, and those data are going to be coming out in the coming year.
Phillip Koo: So when you look to the next decade, or next two decades-
Nick James: Yes.
Phillip Koo: ... where do you think you need to go? Where will the biggest impact occur with STAMPEDE?
Nick James: Well, I think, we're going to get a huge... We've got a very, very exciting pipeline of results coming out from all this translational research, which will allow us to understand better why some patients do and some do not respond to drugs like docetaxel and abiraterone. I think that's going to be very important. I think, the lesson of looking at multiple different treatments within a single trial framework, I think, is very important. It's much cheaper than assessing all of these things separately. And much more efficient, because you don't need a control arm for your PARP inhibitor trial, a control arm for your PSMA Lutetium trial, or whatever it is you're choosing to put in your trial.
And so, those are the two things we're going to be assessing next, if you like, the pharmaceutical point of view, but we're also going to be assessing stereotactic radiotherapy for oligometastatic disease at the same time. So we're going to assess three different things simultaneously, in the arms that we have in set up at the moment. So I very much hope those will carry on, shedding insight into how we can improve the outcomes for men with metastatic prostate cancer.
Phillip Koo: Great. That's wonderful. So many words of wisdom here. I think, there's no doubt many researchers here in Latin America will be inspired by this, and hopefully, we will see offshoots of this type of work throughout the world. So thank you.
Nick James: Thank you very much.