Optimal Therapies for Metastatic Hormone-Sensitive Prostate Cancer

Claire Vale, PhD

As part of our coverage of the European Society for Medical Oncology (ESMO) 2017 Congress, we spoke with Claire Vale, PhD, a senior research scientist within the MRC Clinical Trials Unit and a member of the faculty of population health sciences at University College London in the United Kingdom. Dr. Vale presented a late-breaking abstract on a meta-analysis of optimal systemic therapy options for men with metastatic hormone-sensitive prostate cancer.

Cancer Network: First, can you tell us about the current treatment options for patients with metastatic hormone-sensitive prostate cancer?

Dr. Vale: The standard-of-care treatment for men with advanced hormone-sensitive disease had been hormone therapy or androgen deprivation therapy (ADT) for many years, but in the last few years there have been a number of randomized trials that have looked at different treatments in addition to the standard of care. About 2 years ago, there were some key trial results, of which we did a meta-analysis, and they showed that adding docetaxel to ADT improved the survival of men with metastatic disease. Subsequently, docetaxel in addition to ADT has become the standard of care for these men. Earlier this year at the American Society of Clinical Oncology Annual Meeting in June, the results of the LATITUDE and STAMPEDE trials showed that adding a new combination treatment, abiraterone acetate plus prednisolone, to ADT has a survival advantage for these men, but that treatment has yet to be thought of as standard. In most cases, docetaxel in addition to hormone therapy is the current standard of care, but abiraterone has also been shown to be beneficial.

Cancer Network: Can you tell us about the design of your meta-analysis, called STOPCaP?

Dr. Vale: STOPCaP is a collaboration from the team that I work with at the MRC Clinical Trials Unit at University College London. We are reviewers and researchers and have been bringing a group of clinicians and statisticians together to conduct a series of systematic reviews or meta-analyses in hormone-sensitive prostate cancer. We already reported the results of a meta-analysis looking at the addition of either zoledronic acid or docetaxel chemotherapy to ADT at the start of 2016. Earlier this year, one of my colleagues, also under the STOPCaP collaboration, reported the results of a systematic review of adding the abiraterone-plus-prednisolone combination to ADT.

The meta-analysis we presented at ESMO is actually a network meta-analysis, which is different in that it brings together all of the trials that have looked at all of the different treatments that have been tested with ADT. Importantly, in the setting of metastatic prostate cancer, what a network meta-analysis allows us to do is to use all of the trial results to get an indirect comparison of the different treatments, so that we can start to get some sense of the ranking of how good or indifferent these treatments are in this setting. This is important because with the exception of some of the data coming out of the STAMPEDE trial, there are no other head-to-head comparison data looking at the two effective treatments of docetaxel or abiraterone plus prednisolone in combination with ADT. There are no trials that compare these regimens directly. The network meta-analysis does give us an option to compare these two treatments in an indirect way. We brought together the data from all of the reported studies, 6 trials in total, which include more than 6,000 men.

Cancer Network: What are the most important results you and your colleagues found when you did the meta-analysis?

Dr. Vale: Our results reiterate and support some of the things that we already knew. We showed, again, that adding abiraterone or docetaxel or a combination of zoledronic acid and celecoxib given alongside ADT each had a survival advantage. So, there is no real surprise there. What our results showed that was novel was that there was a very high probability that abiraterone acetate was the best of the treatments, in terms of survival-we saw a 93% probability that abiraterone was the best treatment, and a 100% probability in terms of failure-free survival. Docetaxel had the second highest probability of being the best treatment. What we are not sure of now is how big of a survival advantage abiraterone might have over docetaxel, when both are combined with ADT.

Cancer Network: What is next for you and your colleagues? Are there more data to analyze as part of this larger meta-analysis, and are you planning any follow-up work on the questions raised by your study results?

Dr. Vale: We certainly are following up, and with the STOPCaP collaboration, we’ve got plans to further this work. It is worth mentioning again that the results we presented at ESMO are based on just the reported data from these studies and any meta-analysis that uses reported data is quite specific-there is not an awful amount of flexibility in the analysis that we can conduct. The next big step in our collaboration is to go back to the trialists who we were working with and work together to collect and re-analyze the individual participant data. And by doing that, we should be able to get a much more detailed analysis of the effects of the treatments. For example, it is possible that the treatments may be more or less effective in different patient groups defined by disease or baseline characteristics, and collecting individual participant data will enable us to take all of those things into account and get a much better sense of which of these treatments work best and in who. There are also other things that we might need to take into account, such as any changes in progression or outcomes that have happened over time, because all of these trials were not done at the same time, and we hope to address some of the remaining uncertainties.

Cancer Network: Thank you so much for joining us today, Dr. Vale.

Dr. Vale: No problem, thank you for having me.