1. High risk localized (T3/T4, PSA >40 or Gleason score 8-10)
2. Node positive PC
3. Newly diagnosed metastatic disease (M1)
4. High risk recurrence post-surgery or radiotherapy (RT)
Dr. James continued his presentation by briefly discussing the setting of large phase 3 trials in the UK, such as the STAMPEDE trial, that has recruited more than 9000 patients thus far. These trials demand years of investment from the key players, usually taking 5-10 years from idea to result, involving hundreds or thousands of patients, hundreds of research staff, and cost millions in development. More importantly, there is only a 33% chance of the new experimented treatment to actually be better.
Due to these significant limitations, the relative novel multi-stage trial design was developed in STAMPEDE. In contrast to the traditional trial approach, the multi-arm, multi stage approach allows researchers to enroll more patients to different experimental arms, with the same number of patients required for the control group, thus increasing patients’ chance to be recruited to an experimental rather than a control arm.
Moving on, Dr. James summarized what we have learned so far from the experience of the STAMPEDE trial:
1. Adding arms to a study is fast and feasible – recruitment of patients in every added arm since STAMPEDE began has been faster and better.
2. Impact of RT on high risk and node positive disease. In node negative disease, failure free survival (FFS) was better with RT (HR 0.33, 95% CI 0.18-0.61). More importantly, in node positive disease FFS was also better with RT (HR 0.51, 95% CI 0.31-0.84). These results strongly support usage of RT in node positive PC.
3. Docetaxel improves survival in hormone naïve prostate cancer (HNPC) (for FFS HR 0.62, 95% CI 0.54-07, p<0.0000000001, and for overall survival- HR 0.76, 95%CI 0.63-0.91, p=0.003). When looking specifically at M1 patients receiving Docetaxel, survival was better with HR 0.73 (95% CI 0.59-0.89, p=0.002). Docetaxel also reduced skeletal related events (HR 0.6, 95% CI 0.48-0.74, p=0.00000127).
4. Zoledronic acid does not improve survival or skeletal related events in HNPC (HR 0.93, p=0.44), and (HR 0.89, 95% CI 0.73-1.07, p=0.221), respectively.
4. Publishing positive results does not mean immediate implementation of results, and therefore requires lobbying for fast implementation.
5. And just recently, Abiraterone also improves survival and FFS in HNPC with a 37% improvement in survival (HR 0.63, 95% CI 0.52-0.76, p=0.00000115), and 71% improvement in time to failure (HR 0.29, 95% 0.25-0.34, p=0.37*10-61). Lastly Abiraterone also reduced skeletal related events by 55% (HR 0.45, 95% CI 0.36-0.58).
Dr. James concluded his intriguing presentation with some predictions on what we are going to learn in the future, including the effect of docetaxel in high versus low volume metastatic disease, RT in HNPC (pending results in 2018), Abiraterone versus Enzalutamide comparison (pending results in 2020), estrogen patches (pending 2021), Metformin (pending 2024), Rucaparib in BRCA+ disease (in set up), and in planning for the future: Radium 223 and androgen receptor blockade, PD1 blockade, and radical therapy for oligometastatic disease. Incorporation of results from all these future analyses will greatly change PC management strategies in the near future.
Presented By: Nicholas D. James, BSc, MBBS, PhD, University of Birmingham and Queen Elizabeth Hospital, Birmingham, UK
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA