Episode 19: Relugolix as hormone therapy for men with advanced prostate cancer: results from the HERO trial

In this new episode of ‘What’s New Doc’ in 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 recently reported quality of life (QoL) data of the phase III HERO trial, comparing the GnRH antagonist relugolix to the standard GnRH agonist leuprolide in patients with advanced prostate cancer.¹

In the HERO study, relugolix proved to be associated with a significantly better testosterone suppression than leuprolide. Furthermore, also the testosterone recovery in patients who discontinued ADT happened faster with relugolix than with leuprolide. In terms of cardiovascular risk (CV), a controversial topic in the context of ADT, relugolix proved to be associated with a 54% lower risk for a major adverse CV event compared to leuprolide.² No significant differences were seen between both agents in terms of QoL. During the testosterone recovery phase, however, hormonal treatment–related symptom scores were somewhat lower for relugolix than for leuprolide, which is probably related to the more rapid testosterone recovery after treatment cessation with relugolix.

On the testosterone recovery, Prof Joniau acknowledged that about half of the patients who receive long-term ADT (18-24 months) with a GnRH agonist never get back to normal testosterone levels, which has an important impact on their sexual function. While HERO indicates a more rapid recovery with relugolix, it remains to be seen whether this will still be the case if it is used for a longer period of time.

With respect to CV risk, Prof Tombal and Prof Joniau underscored that the available data on the increased risk for CV events with GnRH agonists are inconclusive at best and mainly point towards an increased CV risk in patients who recently suffered a severe CV event (i.e., myocardial infarction, stroke).^3-6 In their opinion, there is no real difference in the CV risk with GnRH agonists and antagonists in the majority of patients. In the small subset of patients with a high CV risk (i.e., ischemic event in the last year), the potential benefit of ADT has to be weighed against the risks. When this patient has an intermediate risk prostate cancer, it is probably wise to forego on ADT altogether. If the prostate cancer is high risk, a GnRH antagonist is likely the better choice.