ESMO 2017: What are the optimal systemic treatments for men with metastatic, hormone-sensitive prostate cancer? A STOPCaP systematic review and network meta-analysis
For this study, overall survival (OS) data from completed reviews of docetaxel, zoledronic acid and abiraterone + prednisone/prednisolone and from recent trials of zoledronic acid and celecoxib contributed to the aggregate data network meta-analysis. Correlations between treatment comparisons within multi-arm multi-stage trials (e.g. STAMPEDE) were estimated from control-arm event counts in overlapping recruitment periods. The authors assumed network consistency and a common heterogeneity variance.
Network estimates of effects on OS were consistent with reported comparisons with ADT alone for: abiraterone + prednisone/prednisolone (HR = 0.61, 95%CI 0.51-0.76); docetaxel (HR = 0.74, 95%CI 0.65-0.85); celecoxib + zoledronic acid (HR = 0.77 95%CI 0.62-0.96) and docetaxel + zoledronic acid (HR = 0.78 95%CI 0.65-0.93). The effect of celecoxib + zoledronic acid is consistent with the additive effects of the individual treatments. Based on the current data, the network OS results suggest that abiraterone + prednisone/prednisolone has the highest probability of being the best treatment, and docetaxel the second-best treatment option. The authors state that a strength of the study is that they included all available results and appropriately accounted for inclusion of multi-arm multi-stage trials in their network meta-analysis.
In conclusion, the authors noted that the results of the current study support the use of abiraterone + prednisone/prednisolone or docetaxel with ADT in men with mHSPC. There is now direct evidence from the STAMPEDE trial presented earlier this meeting [3] that failure free survival and progression free survival clearly favor ADT + abiraterone. Although not statistically significant, ADT + abiraterone also favor metastasis free survival and skeletal related event survival, while overall survival favors ADT + docetaxel [3]. The ongoing PEACE-1 trial (NCT01957436) will corroborate (or otherwise) their relative effects. Dr. Vale also notes that a patient level data network meta-analysis is also in development to fully account for patient variability across trials, changes in prognosis or treatment effects over time, and the potential impact of treatment on progression.
Speaker: Claire L. Vale, MRC Clinical Trials Unit at UCL, London, United Kingdom
Co-Authors: D. J. Fisher (London, United Kingdom) J. Carpenter (London, United Kingdom) I. R. White (London, United Kingdom) S. Burdett (London, United Kingdom) N. W. Clarke (Salford, United Kingdom) K. Fizazi (Villejuif, France) G. Gravis (Marseille, France) N. D. James (Birmingham, United Kingdom) M. D. Mason (Cardiff, United Kingdom) M. K. Parmar (London, United Kingdom) L. H. Rydzewska (London, United Kingdom) C. J. Sweeney (Boston, United States of America) M. R. Spears (London, United Kingdom) M. R. Sydes (London, United Kingdom) J. F. Tierney (London, United Kingdom)
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain
References:
1. Rydzewska LHM, Burdett S, Vale CL, et al. Adding abiraterone to androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer: A systematic review and meta-analysis. Eur J Cancer 2017;84:88-101.
2. Vale CL, Burdett S, Rydzewska LHM, et al. Addition of docetaxel or bisphosphonates to standard of care in men with localized or metastatic, hormone-sensitive prostate cancer: A systematic review and meta-analyses of aggregate data. Lancet Oncology 2016;17(2):243-256.
3. Sydes MR, Mason MD, Spears MR, et al. Adding abiraterone acetate plus prednisolone or docetaxel for patients with high-risk prostate cancer starting long-term androgen deprivation therapy: directly randomized data from STAMPEDE. ESMO 2017 abstr LBA31.