Results of AFU-GETUG-20: A randomised phase 3 trial of adjuvant androgen deprivation therapy with leuprorelin acetate after radical prostatectomy in patients with high-risk localized prostate cancer.

386 Background: After radical prostatectomy (RP), men with an undetectable PSA and specific features (extracapsular extension, seminal vesicle involvement, high Gleason score) are at risk of recurrence. No randomized prospective study has been published with LH-RH agonists in the PSA era. AFU-GETUG-20 is a phase III randomised, open, multicenter trial, designed to evaluate the benefit of adjuvant ADT with leuprorelin acetate for 24 months after radical prostatectomy in patients with high risk of recurrence. Methods: Patients with high-risk features (postoperative Gleason score > 7, or ≥ 7 with presence of high-grade Gleason patterns, or pT3b), R0, N0 or Nx, M0, and postoperative PSA < 0.1 ng/mL after RP were eligible. Patients were randomized 1:1 to leuprorelin acetate for 24 months vs observation. The primary endpoint was metastases-free survival (MFS). Secondary endpoints included overall survival, disease-specific survival, PSA recurrence-free survival, and quality of life. Originally 700 patients (350 in each arm) and 250 events were required to detect an improvement of MFS with a HR of 0.80 with a bilateral Logrank test with α= 0.05 and β= 0.20. An interim analysis was planned to test the null hypotheses at the 125th event (50% of events) but was eventually held given the low accrual rate and the accrual was stopped after 325 patients had been accrued. Results: Of 325 patients enrolled, 322 are included in the ITT population. 160 were randomized to the Leuprorelin arm and 162 to the observation arm. The median age was 64.7 years [range, 46-77 years]. The median follow-up is 96.1 months [93.6-106.1] IC95% in the leuprorelin arm and 97.2 months [91.8-101.4] IC95% in the surveillance arm. There was no statistically significant difference between arms for MFS (HR = 0.63 [0.30-1.30] 95%CI; p-= 0.204). Similar results were found for PSA relapse-free survival (HR = 0.74 [0.47-1.16]; p = 0 .187), overall survival (HR = 1.24 [0.56-2.76; p = 0.596), and specific survival (HR = 0.57 [0.10-3.17]; p = 0.512). Patients in the leuprorelin arm reported poorer HRQoD on EORTC QLQ-C30 global health scales, social function scale, and specific symptoms (fatigue, pain, dyspnoea, and insomnia). Post-hoc contrast analysis showed a difference between the groups during the treatment period. The two groups returned to comparable levels during follow-up (M36 and M48). Conclusions: Using 2 years of ADT after RP in high-risk patients with an undetectable post-operative PSA did not significantly improve MFS in AFU-GETUG-20. That the trial only accrued about half of the planned patients is the main limitation. The limited number of observed metastatic events in this population, although with a long follow-up, emphasizes the need to identify better biomarkers predicting for relapse to select candidate patients for the next generation of trials. Clinical trial information: EudraCT #:2010-022037-29 UC-0160/1003.