Episode 21: Neoadjuvant degarelix with or without apalutamide prior to surgery for high-risk prostate cancer: results of the phase II ARNEO 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 discuss the results of the phase II ARNEO trial, evaluating the combination of degarelix and apalutamide as neoadjuvant therapy for patients with high-risk prostate cancer.¹

In the randomized, placebo-controlled, phase II ARNEO trial, 99 patients with high-risk prostate cancer were randomly assigned (1:1) to receive 12 weeks of neoadjuvant degarelix in combination with either apalutamide or matching placebo.  After neoadjuvant therapy, all patients underwent a radical prostatectomy.

In earlier reports of this trial, the degarelix-apalutamide combination was associated with a significantly higher rate of minimal residual disease prior to surgery (38% vs. 9.1%).¹ During EAU 2024, oncological outcomes of this trial were presented indicating that the improved tumoral downstaging observed with degarelix-apalutamide translated into a (non-significant) 42% decrease in the risk for a biochemical recurrence compared to degarelix alone (22% vs. 36%; HR[95%CI]: 0.58[0.27-1.25]; p= 0.14).² Interestingly, almost none of the patients with MRD prior to surgery suffered a biochemical recurrence, irrespective of the treatment arm.

The positive results of this phase II trial pave the way for larger phase III studies evaluating the role of androgen receptor pathway inhibitors (ARPI) as neoadjuvant therapy for patients with high-risk prostate cancer. To further elucidate the added value of androgen deprivation therapy in this setting, prof Tombal urges to also include a treatment arm in which an ARPI is given as monotherapy in these trials.