In Focus Enza + ADT in patients with high risk BCR

The EMBARK trial was a 3 arm RCT that included patients with BCR post local therapy and randomised them in 1:1:1 to receive Enza + Leuprolide or placebo + Leuprolide or Enza alone. The inclusion criteria was BCR post local Rx with high risk disease (defined as PSA doubling time of <9mo and a PSA level of >2ng/mL after RT or >1 ng/mL after RP), a testosterone of >150ng/dL and an ECOG of 0-1. A pause in Rx was allowed if the PSA became <0.2 at 37 weeks and was restarted if it became 5ng/mL in prev RT or 2ng/mL in prev RP. The primary end point was MFS whereas the OS, PSA progression and time to new anti-neoplastic Rx were secondary end points. A total of 1068 patients were randomised at 244 sites and 17 countries. The authors found that the risk of metastasis or death was 57.6% lower in the combination arm. Also, the freedom from PSA progression at 5 yrs, time to new anti-neoplastic Rx and risk of developing castration resistance was lowest in the combination group. The risk of death was also 41% lower in the combination arm compared to the other arms and the 5yr OS was 92.2% in the combination arm, 87.2% Leuprolide alone and 89.5% in the Enza alone arm. The incidence of adverse events and treatment discontinuations were nearly similar between all 3 groups and the type of adverse events were similar to that already reported. Thus the results of this trial showed that combination of Leuprolide + Enza showed clinical benefit in patients with high risk BCR after local Rx and that Enza monotherapy also faired better than Leuprolide alone in terms of MFS, PSA progression and need for new anti-neoplastic Rx.