What kind of patients with castration-naïve prostate cancer can benefit from upfront docetaxel and abiraterone: A systematic review and a network meta-analysis

We conducted a systematic network meta-analysis to review the relevant literature evaluating the therapeutic efficacy of upfront docetaxel (Doc) or abiraterone (Abi) plus androgen deprivation therapy (ADT) on oncological outcome in patients with castration-naive prostate cancer (CNPC). An attempt to identify subgroups of patients who would benefit most either from Doc or Abi plus ADT and further compare the efficacy and safety between these two combination therapies was made. A comprehensive search of the PubMed/Medline, Embase databases, International Clinical Trial Registration Platform (ICTRP), Clinical Trial, and Cochrane Central Register of Controlled Trials to December 2017 was performed. Six studies, involving 6480 patients, were included in this meta-analysis, consisting of over 60% (4462/6480) of patients with metastatic CNPC (mCNPC, M1), and 31.1% (2018/6480) of patients with non-metastatic CNPC (M0). In total, combination therapies (ADT plus Doc or Abi) significantly improved overall survival (OS) and failure-free survival (FFS) for all CNPC patients. For M1 patients, combination therapies were dramatically associated with improved OS and FFS, but for M0 patients, only with moderate improvement in FFS. M1 patients < 70 years old, Eastern Cooperative Oncology Group (ECOG) performance status (ECOG PS) 0-1, Gleason score (< 8), or visceral metastases could realize better survival benefit from either combination therapy. In indirect comparisons among M1 patients with younger age (< 70 years), ECOG PS 0-1 or aggressive Gleason score (GS ≥ 8), upfront Abi showed superiority to Doc in prolonging FFS. The incidence of severe adverse events (AEs ≥ 3) was comparable between these two therapeutic regimens. In conclusion, upfront Doc or Abi plus ADT should be considered a standard of care in selected patients with mCNPC. For a subset of populations, Abi may be the first choice for men who start treatment for the first time.