Findings from the STAMPEDE trial and STOPCaP study, both looking at how to treat high risk and advanced prostate cancer, were presented this weekend at the European Society for Medical Oncology (ESMO) annual meeting in Madrid. The findings throw light on the relative advantages of adding docetaxel or abiraterone to long-term hormone therapy.
Recent years have seen several major advances in how we treat high risk prostate cancer. Trials, including STAMPEDE, have demonstrated that adding either abiraterone or docetaxel to standard long-term hormone therapy improves survival compared to long-term hormone therapy alone.
Where both treatments are available, a decision needs to be made on which to use as up front therapy.
Abiraterone (also known as abiraterone acetate, or Zytiga) is a type of hormone therapy that works in a different way to standard hormone therapy. It is given as tablets taken every day, and supplemented with a steroid tablet. Docetaxel is a chemotherapy drug, given in hospital intravenously, usually 6 times, 3 weeks apart. A steroid tablet is also given during these weeks.
Both drugs are licensed to treat prostate cancer that has spread and has stopped responding to standard hormone therapy. Trial data, including those from STAMPEDE, have shown that each drug is also beneficial given earlier in the disease, when men are starting long-term hormone therapy for the first time.
Which is best: abiraterone or docetaxel?
Two presentations looked at comparing the benefits of abiraterone and docetaxel, to help doctors and patients choose which treatment is best for them.
The first is an analysis from the STAMPEDE trial, which directly compared men who were recruited to the trial during the same time period (November 2011-March 2013) and randomised to either docetaxel plus standard hormone therapy or abiraterone plus standard hormone therapy. This is the first direct randomised data comparing these two treatments.
189 men were randomised to docetaxel plus standard hormone therapy, and 377 to abiraterone plus standard hormone therapy. 60% of men had disease that had spread beyond the pelvis when they joined the trial. After around four years of follow-up, it seems that men who had abiraterone plus standard hormone therapy did better in terms of delaying the disease getting worse, spreading or having bone problems, but there was no compelling evidence of an improvement favouring either treatment in terms of overall survival. The proportion of men reporting at least one severe side-effect was similar on the two treatments, although the side-effects were different for the two drugs.
The second presentation was from a network meta-analysis as part of the STOPCaP programme. The network meta-analysis, which allows treatments that may not have been directly compared to each other in randomised trials to be compared indirectly, was based on the reported results from six trials, including six separate comparisons from STAMPEDE. More than 6000 men had contributed to these trials overall.
Based on the current data, abiraterone plus standard hormone therapy is most likely to be the best treatment. Docetaxel is likely to be the second best. However, it is still not certain how much better abiraterone is than docetaxel in terms of improving the survival of men with advanced prostate cancer.
Other treatments that recent trials have published results for (zoledronic acid or celecoxib), and standard hormone therapy alone, are likely to be the least effective treatment options compared in the network meta-analysis.
These results support the use of abiraterone or docetaxel for men whose prostate cancer has spread, and who are starting long-term hormone therapy for the first time.
The STOPCaP team is developing the network meta-analysis using individual participant data to allow them to take account of differences in patient characteristics in the different trials, and changes in prognosis or treatment effects over time.
How effective is abiraterone for men whose prostate cancer has not spread beyond the pelvis?
One of the analyses presented at the ESMO annual meeting this weekend was further results from the STAMPEDE trial, looking at the effectiveness of adding abiraterone for men whose disease had not spread beyond the pelvis when they joined the trial.
915 men who were starting long-term hormone therapy for the first time, and whose disease had not spread beyond the pelvis, were randomised to have either standard hormone therapy alone, or abiraterone plus the steroid prednisolone plus standard hormone therapy. The average age of men joining this comparison in the trial was 67 years old, and they were followed up for just over three years, on average.
For men whose disease had not spread to their nodes or further beyond the pelvis, abiraterone significantly improved the length of time before their treatment stopped working. Treatment was still working after three years for 82% of men in the standard hormone therapy plus radiotherapy group, compared to 98% of men who had both abiraterone and standard hormone therapy plus radiotherapy. We do not yet have enough data to say whether this improvement with abiraterone will affect whether these men live longer.
For men whose disease had spread to their pelvic nodes, but not further beyond their pelvis, abiraterone also improved the length of time before their treatment stopped working, and also seemed to improve how long men lived for. Outcomes in these patients were better if they were also planned for radiotherapy. The planned use of radiotherapy in N+M0 patients has been steadily increasing over time in STAMPEDE; these data may further encourage its use.
The STAMPEDE trial will continue to follow-up these men, to find out how well they do in the longer term.