Randomized controlled trial of GnRH antagonist monotherapy versus GnRH agonist plus bicalutamide (CAB) for patients with metastatic hormone-sensitive prostate cancer (mHSPC) (KYUCOG-1401).

Abstract

99 Background: To investigate a clinical response of GnRH antagonist monotherapy against CAB therapy for mHSPC. Methods: Histopathological confirmed mHSPC patients were randomly assigned to GnRH antagonist monotherapy group (Group A) and CAB group (Group B). A deferred CAB therapy by adding bicalutamide to GnRH antagonist was performed in Group A after PSA progression. The primary endpoint was PSA progression free survival (PSA-PFS). The secondary endpoints were time to CAB treatment failure (CAB-TTF), radiographic progression free survival (rPFS), overall survival (OS), change of PSA, effect on hormone dynamics, change of bone metabolic markers, effect on lipid metabolism, adverse events (AE). This trial was registered with UMIN-CTR (UMIN000014243). Results: A total of 200 patients (101 patients in Group A and 99 in Group B) were registered from June 2014 to June 2017. The PSA-PFS was significantly better in Group B (HR (95% CI) =1.40 (1.01-1.95), p=0.041) as shown in the table. Time to CAB treatment failure (TTF) tended to be better in Group A, but there was no statistically significant difference in CAB-TTF between two groups (Table). rPFS and OS were also not statistically significant difference (Table). Time to PSA nadir was significantly shorter in Group B (HR (95% CI) = 0.72 (0.54 - 0.97), p = 0.028). The proportion of patients whose serum testosterone did not reach or maintain the castration level was more frequent in Group A (significant difference at 60 weeks, p = 0.046). There was no significant difference in the effect of bone metabolic markers and lipid metabolism between two groups. In terms of AE, injection-site-reaction was more frequent in Group A. Conclusions: LH-RH agonist CAB therapy (Group B) prolonged PSA-PFS compared to LH-RH antagonist monotherapy (Group A), probably due to the higher frequency of insufficient achievement of castration level in Group A. However, a deferred CAB therapy by adding bicalutamide to GnRH antagonist resulted in no difference in CAB-TTF, rPFS and OS. Clinical trial information: UMIN000014243.[Table: see text]