Post radical prostatectomy (RP) PSA outcomes following 6 vs 18 months of perioperative androgen deprivation therapy (ADT) in men with localized high risk prostate cancer (LHRPC): Results of Part 2 of a randomized phase 2 trial.

Abstract

5095 Background: Patients with LHRPC have an increased risk of relapse following RP. We previously reported on Part 1 of a phase 2 trial testing neoadjuvant apalutamide, leuprolide, and abiraterone acetate plus prednisone (ALAAP) or leuprolide and abiraterone plus prednisone (LAP) for 6 months followed by RP (McKay, J Urol, 2021). We demonstrated favorable pathologic responses (tumor <5 mm) at RP in 20.3% of patients (n=24/118). Herein, we report the results of Part 2 testing adjuvant ALAAP (NCT02903368). Methods: Eligible patients had a Gleason score ≥4+3, PSA >20 ng/mL, or T3 disease (by DRE or MRI) and lymph nodes <20 mm. At Part 2, patients were randomized 1:1 to ALAAP for 12 months (Arm 2A) or observation (Arm 2B), stratified by neoadjuvant therapy and pathologic T stage (<ypT3 or ≥ypT3). The primary endpoint was biochemical progression-free survival (bPFS) at 3 years post-RP. bPFS was defined as the time from randomization to progression (PSA ≥ 0.2 ng/mL, local/distant disease on CT/MRI or bone scan, or receipt of post-RP therapy or radiation for rising PSA) or death. The Kaplan-Meier estimate of bPFS at 3 years was compared between arms using a Chi-square test (Klein, Stat Med, 2007). Secondary endpoints included safety and time to testosterone recovery (>200 ng/dL). Results: Overall, 82/118 (69%) of patients enrolled to Part 1 were randomized to Part 2. Median follow-up was 47 months post-RP. Patient preference was the main reason for non-randomization in Part 2. In the intent-to-treat analysis, the 3-year bPFS estimate was 80% (95% CI:65-90%) for Arm 2A and 72% (95% CI:56-84%) for Arm 2B, which was not statistically significant (2-sided p=0.39). Patients who achieved pathologic responses (n=14) had longer bPFS than non-responders (log-rank test two-sided p=0.03; 3-year bPFS 100% vs 72%). In per-protocol population, of 36 patients receiving Arm 2A treatment with available data, 83% had testosterone recovery and median time to recovery from therapy end was 8.7 months. For patients on observation (n=42), 95% had testosterone recovery, and median time to recovery from RP was 4.0 months. No new safety signals were observed. Conclusions: Neoadjuvant ADT in LHRPC resulted in favorable pathologic responses and 3-year bPFS in a subset of patients. As 30% of patients declined an additional 12 months of adjuvant treatment, the study was underpowered to detect a difference between 6 months vs. 18 months of treatment. Subsequent analyses will evaluate predictors of improved bPFS. Clinical trial information: NCT02903368 . [Table: see text]