He acknowledged the STAMPEDE investigators and talked about how there was a “need for speed and a new approach” to test new drugs especially in prostate cancer where the demand for evaluation of new therapies was large. Since the process of developing and starting a new trial is time-consuming, simultaneous assessment of a number of research treatments against a single control arm-MAMS approach was proposed (Figure 1).
Dr. Clarke then highlighted the advantages of MAMS trial design, which includes that fewer patients are needed for the control treatment, greater number of treatments can be tested with a limited number of patients, can add interim analyses and at the interim analyses, modifications can be made based on the results of the trial so far. Adding arms to the study is fast and feasible which was done in the STAMPEDE trial at various stages.
Dr. Clarke then highlighted some of the published studies from STAMPEDE trial. James et al. published in JAMA oncology in 2016 showing survival for men entering the cohort with high-risk M0 disease was higher than anticipated at study inception. These nonrandomized data were consistent with previous trials that support the routine use of RT with HT in patients with N0M0 disease. Additionally, the data suggest that the benefits of RT extend to men with N+M0 disease. James et al. published in Lancet in 2015 showing that Zoledronic acid showed no evidence of survival improvement and should not be part of the standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of the standard of care for adequately fit men commencing long-term hormone therapy. These positive studies have changed the treatment paradigm and influenced change in clinical guidelines. Dr. Clarke also highlighted their study in NEJM in 2017 which concluded that among men with locally advanced or metastatic prostate cancer, ADT plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure-free survival than ADT alone. Some of the recent data from STAMPEDE trial which was published in Lancet was also presented. Radiotherapy to the prostate improves overall survival in men newly diagnosed with metastatic prostate cancer who have a low metastatic disease burden but not in those with a higher burden of disease. He also provided information on new trial arm proposal to investigate the treatment of men with newly presenting oligometastatic prostate cancer.
Dr. Clarke then concluded his talk by emphasizing that STAMPEDE and the MAMS model will produce a new major result every 12-18 months and by 2020, this platform will have answered 11 major questions in 20 years. STAMPEDE has now recruited 10,000 participants and has shown that such trials are feasible and practicable, recruit well enough to overcome more arms, and a number of other clinical trials are adopting this model.
Presented by: Noel Clarke, ChM, FRCS(Urol), The Christie and Salford Royal Hospitals, Salford, United Kingdom
References:
1. James ND, Sydes MR, Clarke NW, et al: Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet 387:1163-77, 2016
2. James ND, Spears MR, Clarke NW, et al: Failure-Free Survival and Radiotherapy in Patients With Newly Diagnosed Nonmetastatic Prostate Cancer: Data From Patients in the Control Arm of the STAMPEDE Trial. JAMA Oncol 2:348-57, 2016
3. Gillessen S, Gilson C, James N, et al: Repurposing Metformin as Therapy for Prostate Cancer within the STAMPEDE Trial Platform. Eur Urol, 2016
4. James ND, Spears MR, Clarke NW, et al: Survival with Newly Diagnosed Metastatic Prostate Cancer in the "Docetaxel Era": Data from 917 Patients in the Control Arm of the STAMPEDE Trial (MRC PR08, CRUK/06/019). Eur Urol 67:1028-38, 2015
5. Attard G, Sydes MR, Mason MD, et al: Combining Enzalutamide with Abiraterone, Prednisone, and Androgen Deprivation Therapy in the STAMPEDE Trial. Eur Urol, 2014
6. Sydes MR, James ND, Mason MD, et al: Flexible trial design in practice - dropping and adding arms in STAMPEDE: a multi-arm multi-stage randomised controlled trial. Trials 12 Suppl 1:A3, 2011
7. Sydes MR, Parmar MK, James ND, et al: Issues in applying multi-arm multi-stage methodology to a clinical trial in prostate cancer: the MRC STAMPEDE trial. Trials 10:39, 2009
8. Parmar MK, Barthel FM, Sydes M, et al: Speeding up the evaluation of new agents in cancer. Journal of the National Cancer Institute 100:1204-14, 2008
9. James ND, de Bono J, Spears MR, Clarke NW, et al: Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. NEJM 2017
Written by: Abhishek Srivastava, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Philadelphia, Pennsylvania, @shekabhishek, at the 19th Annual Meeting of the Society of Urologic Oncology (SUO), November 28-30, 2018 – Phoenix, Arizona