A Phase II Randomized, Open-Label Study Comparing Salvage Radiotherapy in Combination with 6 Months of Androgen-Deprivation Therapy with LHRH Agonist or Antagonist Versus Anti-Androgen Therapy with Apalutamide in Patients with Biochemical Progression after Radical Prostatectomy

Background Salvage radiotherapy (SRT) is a potentially curative option for patients with rising PSA (biochemical recurrence) after radical prostatectomy. Recently, success rates of SRT were significantly improved through the use of concomitant anti-androgen (AAT) or androgen-deprivation (ADT) therapy. In RTOG 96-01, 2 years of bicalutamide 150 mg resulted in a 5% OS benefit at 12-years. In GETUG-AFU 16, 5-year progression-free survival was significantly improved when SRT was combined with 6 months of an LHRH agonist. Based on GETUG-AFU 16, most European urologists and (radiation) oncologists now combine SRT with at least 6 months of ADT. However, ADT comes with several serious side-effects, both physical (cardiovascular, metabolic, musculoskeletal) and psychological (sexual, emotional and cognitive). Considering RTOG 96-01, and in view of new AAT options, it appears worthwhile to look for alternatives. In that respect, apalutamide (ERLEADA®), a next-generation anti-androgen, is an interesting candidate. Trial design This is a phase II randomized, open-label study comparing SRT in combination with 6 months of LHRH (ant)agonist (arm A) versus 6 cycles of apalutamide 240 mg daily (each cycle is 28 +/- 2 days) (arm B) in hormone-naive patients with biochemical recurrence (PSA > 0.1 µg/L at least 8 weeks after radical prostatectomy). Patients with severe erectile dysfunction are excluded. All subjects will receive SRT as standard of care and will be randomly assigned in a 1:1 ratio to arm A or B. Primary objective is to compare sexual function, based on the EPIC-26 sexual domain score, at 9 months (i.e. 3 months after the end of hormonal treatment). Secondary endpoints include general quality of life (EPIC-26, EORTC QLQ C30 and PR25, FACT-P), acute as well as late toxicity (CTCAE version 5.0), and PSA (complete) response rates (i.e. decline from baseline in PSA level of 80% (90%) or greater). The trial was approved by the local ethics committee on April 2nd 2019 and started recruiting immediately thereafter. Clinical trial identification NCT03899077; 2018-004365-13. Legal entity responsible for the study GZA Hospitals. Funding Janssen. Disclosure All authors have declared no conflicts of interest.