Abstract 588P
Background
Enzalutamide (ENZ) and abiraterone acetate plus prednisone (AAP) are both androgen receptor targeting treatments for metastatic castration-resistant prostate cancer (mCRPC). AAP inhibits the androgen production, whereas ENZ blocks the androgen receptor signalling. Herein, we evaluate and compare treatment changes in serum androgens for ENZ and AAP.
Methods
First-line ENZ (160 mg/day) and AAP (1000 mg abiraterone acetate and 10 mg prednisone/day) for mCRPC were compared in this investigator-initiated open-labelled randomised (1:1) phase IV trial. Eligible patients had progressive metastatic prostate cancer on androgen deprivation therapy (testosterone <1.7nmol/L). Fasting serum androgens, including testosterone and precursors to testosterone (androstenedione, dehydroepiandrosterone sulphate [DHEAS] and 17-Hydroxyprogesterone [17-OHP]), were measured by the gold standard assay liquid chromatography – tandem mass spectrometry before 11 am at baseline and at 12-week post-intervention. The treatment difference in changed androgens was compared with mixed models analysis, and the within-subject change for each treatment group was analysed with paired samples t-test. This was a pre-planned secondary endpoint (EudraCT 2017-000099-27).
Results
From June 2017 to September 2019, 170 participants were randomized to receive ENZ (n=84 analysed) or AAP (n=85 analysed). A larger decline in testosterone, androstenedione and DHEAS was found for AAP than ENZ. In the ENZ group, testosterone and DHEAS increased from baseline to week 12, whereas decreased in the AAP group. No treatment difference was found for 17-OHP (Table). Table: 588P
| Enzalutamide | Abiraterone | Treatment difference Mean (95 CI%) | |||
| Baseline Mean (SD) | 12 week-change Mean (95 CI%) | Baseline Mean (SD) | 12-week change Mean (95 CI%) | ||
| Testosterone (nmol/L) | 0.37 (0.23) | 0.15 (0.10; 0.20) P<0.0001 | 0.34 (0.21) | -0.23 (-0.28; -0.19) P<0.0001 | -0.40 (-0.46; -0.34) P<0.0001 |
| Androstenedione (nmol/L) | 1.74 (0.92) | 0.10 (-0.07; 0.26) P=0.2 | 1.53 (0.84) | -1.24 (-1.41; -1.06) P<0.0001 | -1.44 (-1.63; -1.25) P<0.0001 |
| Dehydroepiandrosterone sulphate (μmol/L) | 1.66 (1.37) | 0.12 (0.02; 0.23) P=0.02 | 1.69 (1.42) | -1.60 (-1.89; -1.32) P<0.0001 | -1.71 (-1.91; -1.51) P<0.0001 |
| 17-Hydroxyprogesterone (nmol/L) | 0.78 (0.58) | 0.062 (-0.07; 0.20) | 0.61 (0.43) | 0.042 (-0.10; 0.18) | -0.12 (-0.30; 0.05) |
Conclusions
In men on androgen deprivation therapy, with remaining androgens mainly derived from the adrenal production, ENZ and AAP both inhibit the androgen stimulation of prostate cancer, but by different mechanism of action resulting in different androgen profiles.
Clinical trial identification
EudraCT 2017-000099-27.
Editorial acknowledgement
Legal entity responsible for the study
J. Sønksen.
Funding
This trial was mainly supported by funding from Herlev and Gentofte University Hospital. Additional grants were received from the following independent foundations: Scandinavian Prostate Cancer Group research fund, Herlev and Gentofte internal research fund, ‘Torben og Alice Frimodts’ foundation, and ‘Christina Larsen og Dommer Ellen Larsen’ Scholarship.
Disclosure
M. Fode: Other, Advisory Board: Ferring; Other, Advisory Board: Astellas. H. Lindberg: Other, Advisory Role: MSD; Financial Interests, Advisory Role: Janssen; Financial Interests, Advisory Role: Sanofi-Aventis. P. Østergren: Financial Interests, Invited Speaker: Astellas; Financial Interests, Invited Speaker: Ipsen; Financial Interests, Invited Speaker: Ferring. All other authors have declared no conflicts of interest.