I was here at ESMO to present data from the STAMPEDE clinical trial. This is a platform protocol using a novel multi-arm, multi-stage platform design. We’ve previously shown, alongside other trials, that adding docetaxel with prednisolone to a standard of care that’s based in long-term androgen deprivation therapy improves survival. We’ve more recently shown that adding abiraterone acetate with prednisolone to the same backbone of androgen deprivation therapy also improved overall survival. So now clinicians have two treatments which they can use with their patients but which should they start with?
People are looking at the literature, they’re looking at the papers and trying to understand which of those treatments they should be starting with. We thought we could help them by presenting the data from STAMPEDE. The docetaxel comparison recruited patients between October 2005 and March 2013; the abiraterone comparison recruited patients between November 2011 and January 2014. So we have this small window, fourteen months, where we had both arms, both research arms, open to recruitment. It’s not fully powered but it is randomised and it is prospectively collected and it’s not small – we had 566 patients. So people are trying to make a decision, these are the only prospective head to head data that are going to be coming out in the foreseeable future so we thought it was important to present this information.
This is why we presented the data, it was there as a late breaking abstract. What we saw was no evidence of a difference in terms of overall survival between these two treatments. In terms of other outcome measures we saw that abiraterone acetate with prednisolone was significantly better in terms of failure free survival, which is a very early outcome driven by rising PSA. We saw also a benefit to abiraterone in terms of progression free survival and some weak evidence in terms of metastatic progression free survival. But when we look at overall survival, prostate cancer specific survival, symptomatic skeletal events, we see no evidence of a difference between the two treatments.
The toxicity profiles for these two treatments are really quite different but they’re quite well-known. So the data we present there isn’t a surprise to anybody, I don’t think. What we showed was about half of the patients on both of those treatments have at least one severe toxicity at some point after randomisation. We can also see that if we look at a safety population of patients who have not relapsed by one year, who have an assessment in that window and who started their allocated treatment, it’s about one in nine patients on both abiraterone and on docetaxel that have a grade 3 or higher toxicity at one year. So even the level, the prevalence, of severe toxicity is very comparable across those two treatments. That’s also the same when we look at two years as well.
An important difference is the pattern of second line and third line and fourth line treatments. So patients who have docetaxel up front are much more likely to move to an AR-targeted therapy although there is some re-challenge with docetaxel. Patients who start with abiraterone are much more likely to move to docetaxel or to have exposure to docetaxel but there is some exposure to AR-targeted therapies. So it becomes almost an immediate versus deferred question.
I suppose the question there is clinicians and patients who are making that choice now, does it just come down to whether they think there is the risk for those toxicity related events you mentioned or quality of life or just go for one of them?
As a statistician I want to make sure that I’m helping to provide these data from which clinicians, together with their patients, can make a choice that they’re comfortable with for the management of that patient’s care. So I hope that the data we’ve provided here allows a good, sensible discussion for people to make a choice where both of those drugs are available. At the moment docetaxel is not available everywhere, abiraterone is not available everywhere. This may provide some reassurance that the choice that they’re making, that single choice, is OK. Where people have access to both treatments we hope this will allow them to make a sensible and informed decision.
We have a paper which is about to be submitted looking at the cost effectiveness data from docetaxel which is going to be really important. I can’t talk about those data yet. The abiraterone cost effectiveness data are going to be developed at the moment. Whether we’d like it to be or not, I would anticipate that cost is likely to be the driving factor behind that clinical choice as well.