Thank you very much and thank you for the opportunity to present these data today. So I’m presenting this on behalf of my co-investigators and co-authors for the STAMPEDE trial.
The setting is slightly different from what you’ve just heard from Karim. Basically men starting hormone therapy for the first time for a long-term treatment has been one of the mainstays of treatment since the 1940s. We also know over the last couple of years that abiraterone has been shown to prolong survival in men relapsing after first line therapy. The hypothesis we were testing in this particular piece of STAMPEDE is that early use of abiraterone at inception of therapy may give a larger absolute benefit in overall survival than saving the same agent up for later on when the patients have relapsed. As Karim said, we previously showed very similar results with docetaxel in the same patient population at this meeting two years ago.
STAMPEDE is itself an interesting trial, quite apart from the results. It has a multi-arm, multi-stage methodology to it. The multi-arm facet means that we can test multiple different treatments in series and in parallel rather than just having an a versus b format which you endlessly replicate meaning every time you want to ask a new question you have to set up a new trial. So we added abiraterone to the STAMPEDE trial by amending the protocol rather than by setting up a new trial. So it’s a multi-arm format. This can be viewed as like running lots of trials at once, it gives you a higher chance of success. Multiple arms mean more patients get novel therapies and fewer patients get the control therapies which we have found in the clinic turns out to be very attractive to patients. It gives quicker and much more economical answers to multiple questions. So in this particular case we’re presenting data with 40 months of follow-up on 2,000 men, so actually a larger cohort of patients than are presented in LATITUDE.
The multi-stage format means that we check as we go along whether an arm is sufficiently active to merit continued recruitment. So you can view this as being like a high jump contest – in order to stay in the competition the bar goes up and you have to keep jumping over the bar otherwise you’re removed from the trial. So so far we’ve had to remove two arms from the trial prior to completion of recruitment because of insufficient activity. This is the sixth combination from the trial for which we are reporting mature overall survival data and we have overall recruited 9,000 men to the trial as a whole.
For this particular bit of the trial we have an allocation ratio of one patient in the control arm to one patient in the research arm. We were targeting a 25% relative improvement in overall survival. We didn’t publish the interim analyses but they all met their preset criteria for activity and this is the main analysis on the primary outcome measure which is overall survival. Patient characteristics are broad and essentially we set out to define a population that were starting long-term hormone therapy for the first time. The case mix we actually ended up with looks like this, so the median age was 67 years with a big range – 39 up to 85 years. 78% were able to carry out normal activities daily; 52%, just over half, had metastatic disease so this is one of the key differences between this trial and LATITUDE; around 88% of these patients had bone metastases. Even within the metastatic population we have a broader spread of patients, we didn’t just have the high risk we had the whole spectrum. Of the non-metastatic patients they were 48% of the total with the disease confined to the prostate with high risk characteristics like a high PSA or confined to pelvic lymph nodes. 95% of the patients were newly diagnosed so a small number had had previous radical surgery or radiotherapy and then relapsed.
Rather like with the LATITUDE trial we’re showing a highly positive result, so a hazard ratio of 0.63 with a highly significant p-value. This is a 37% relative improvement in survival so at three years this means the survival goes from 76% to 83%. Because we have a broader range of patients we’re nowhere near the median survival for the control arm, let alone for the experimental arm. I haven’t shown you the data here but our projections are that for the experimental arm, for the metastatic part of the comparison, the median survival is going to go from around 3½ years in our population to 6½ years for the abiraterone. So we think this is one of the biggest survival gains ever reported in a trial of an adult solid tumour.
This is the most technical slide I’m going to show you, it’s a Forest plot of the split by metastatic status. For the M0 patients we actually have very few deaths. This is the point estimate of the hazard ratio for the whole trial of 0.63; this is the confidence for the whole trial; this is for the metastatic patients; this is for the non-metastatic patients. As you can see, the effect on survival, even though there are very few deaths so far in the non-metastatic patients it’s very similar. So we think the survival data apply to the whole trial population, not just the metastatic ones. This is the hypothesis we set out to test, it’s a positive trial for the whole population.
Moving on to failure free survival, very similarly to the LATITUDE trial we see a very impressive effect on failure free survival, there’s a hazard ratio of 0.29. I draw your attention to the p-value which has 61 leading zeros prior the first significant figure. This is a 71% improvement in time to treatment failure which at three years translates into a rise from 45% to 75%. Another important outcome, very important for patients, is skeletal related events; this is pain leading to radiotherapy, pathological fracture, surgery to bone, spinal cord compression. This is the skeletal related events for the metastatic subpopulation, you can see we’ve got a hazard ratio of 0.45, that’s a 55% reduction in significant skeletal morbidity. We think this is extremely important to patients and very good news.
So our conclusions are that abiraterone acetate and prednisolone, or prednisone, improves survival for men with hormone naïve prostate cancer starting long-term hormone therapy for the first time. Non-metastatic and metastatic, we think it applies equally to both. I haven’t shown you the adverse events but as with LATITUDE these pretty much coincide exactly with the data seen in the relapsed setting. My final slide is we produced an infographic of how this stacks up and if you look over here you can see on the standard therapy a substantial proportion of the men have died, far fewer on abiraterone, but very strikingly is far more patients have relapsed and obviously these patients are going to go on and die as well, far fewer have relapsed over here. So we think these survival results are rock solid and we also saw a 54% reduction in bone problems. There was an increase in the rate of the serious adverse events, very similar to what you’ve just seen reported for LATITUDE, mostly things like hypertension and transaminase changes. Thank you for your attention.