Episode 13: Enzalutamide for biochemically recurrent prostate cancer: reflections on the EMBARK trial

In this first episode of WND Prostate cancer, Prof Bertrand Tombal from the Cliniques Universitaires Saint-Luc in Brussels and Prof Steven Joniau from the University Hospitals Leuven share their thoughts on the results of the phase III EMBARK trial.

In EMBARK, a total of 1,068 prostate cancer patients with high-risk disease and a biochemical recurrence after local therapy were randomly assigned to receive the androgen receptor targeting agent (ARTA) enzalutamide plus androgen deprivation therapy (ADT), placebo plus ADT or enzalutamide monotherapy.¹ For this trial, high risk disease was defined as a prostate specific antigen (PSA) doubling time of ≤9 months and a PSA level of ≥2 ng/ml above nadir after radiation therapy or ≥1 ng/ml after radical prostatectomy with/without postoperative radiation therapy, a serum testosterone level of at least 150 ng/dl, and an Eastern Cooperative Oncology Group performance-status score of 0 or 1.

The results of EMBARK show that both the combination of enzalutamide and ADT and enzalutamide monotherapy are associated with a significant benefit in metastasis-free survival (MFS) compared to ADT alone. Furthermore, compared to ADT alone, a strong trend for a better overall survival (OS) was seen with enzalutamide, both in combination with ADT and as monotherapy.¹

For Prof Tombal and Prof Joniau these data force the prostate cancer community to rethink the treatment paradigm for patients with a biochemical recurrence following local therapy. In the interpretation of EMBARK they also underscored that this trial was conducted in an era before PSMA-PET was used in the medical imaging for patients with prostate cancer. In this respect, data presented at ASCO 2023 indicated that four out of five ‘EMBARK-like’ patients actually had small tumoral lesions or involved lymph nodes when PSMA-PET imaging was used.² This observation has raised further discussions on how the results of EMBARK should be interpreted.  In the years to come, results of several ongoing trials evaluating ARTA-based therapies in this setting will shed more light on this matter.