Is there a benefit of addition docetaxel, abiraterone, celecoxib or zoledronic acid in initial treatments for patients older than 70 years with hormone sensitive advanced prostate cancer? A Meta-analysis

Background Results from large randomized controlled trials combining docetaxel, abiraterone, celecoxib or bisphosphonates with androgen deprivation therapy (ADT) in hormone-sensitive prostate cancer have emerged. However, in our knowledge, few data are available in patients older than 70 years. Therefore, we undertook a meta-analysis of all published phase III studies. Methods We performed a PubMed search using key-words: “hormone sensitive prostate cancer”, “phase III studies”, “docetaxel”, “abiraterone”, “celecoxib”, “biphosphonates”. We also screened ASCO and ESMO proceedings. Combination therapies were compared with ADT alone. The efficacy outcomes were overall survival (OS) and progression free survival (PFS). Hazard ratios (HRs) with their 95 % confidence interval (CI) were collected from the studies and pooled. A hazard ratio of less than 1.00 favored the combination group. Results This meta-analysis included eight studies: three assess docetaxel (CHAARTED, STAMPEDE arm E and C), two others assess abiraterone (LATITUDE, and STAMPEDE arm G); two others assess celecoxib (STAMPEDE arm D and F) and the last one assesses zoledronic acid alone (STAMPEDE arm B). Our meta-analysis included 2264 patients (86% with metastases). Concerning age, we chose a cut-off of 70 years, corresponding to the available data for each study. The performance index (PS) was 0-1 for about 90% of patients. Overall, in patients > 70 years old, the addition of docetaxel statistically improved PFS (HR = 0.51; CI: 0.42–0.61) but not OS (HR = 0.86; CI: 0.69–1.07). The addition of abiraterone to ADT also statistically improved PFS (HR = 0.49; CI: 0.37–0.64) but not OS (HR = 0.85; CI: 0.67–1.08), as well as the addition of celecoxib (HR = 0.67; CI: 0.53–0.85 and HR = 0.95; CI: 0.73–1.25, respectively). The addition of zoledronic acid did not improved PFS or OS (HR = 0.78; CI: 0.61–1.00 and HR = 0.99; CI: 0.71–1.38, respectively). Conclusions The addition of docetaxel, abiraterone, or celecoxib to ADT significantly increased PFS in older with hormone-sensitive advanced prostate cancer. However the benefit in OS is not statistically significant. Further studies are needed to define the best first-line strategy in this subgroup.