Phase 2, randomized, 3-arm study of abiraterone acetate and prednisone (AAP), AAP plus degarelix (AAP+D), and degarelix (D) alone for patients (pts) with biochemically-recurrent prostate cancer (PC) following radical prostatectomy (RP).

Abstract

Background: Androgen deprivation therapy (ADT) with GnRH analogs does not entirely suppress androgen signaling. AAP + ADT decreases blood and intratumoral testosterone (T) levels by ≥1 log, and in pre‐RP trials resulted in greater pathologic responses relative to ADT alone. Trial designs that can rapidly assess therapies (txs) are critical given the long natural history of PC and resources required for phase 3 trials. Using a novel endpoint (endpt) (undetectable PSA [PSA0] with T recovery [rec]), we hypothesized that AAP+D given in the rising PSA state post‐RP, a low volume but potentially lethal setting, could eliminate all disease, a prerequisite to cure. Methods: Post RP ± salvage radiotherapy pts with a rising PSA ≥1.0 ng/ml, doubling time ≤9 months (mo), no metastases (met) on CT/bone scan, and T ≥150 ng/dl were eligible [NCT01751451]. Prior ADT ≤8 mo was allowed. Pts were randomized (1:1:1) to AA 1000 mg + P 5 mg QD (Grp 1), AAP + monthly D (Grp 2), or monthly D (Grp 3) for 8 mo, followed by cessation of txs. The primary (1 ) endpt was PSA0 with T > 150 at 18 mo and secondary, PSA0 at 8 mo. Results: 120 pts were treated; 113 were evaluable for the 1 endpt; 7 had PSA0 at 18mo without T rec. No difference was seen in PSA0 at 8 mo with AAP vs AAP+D (p > 0.99), or AAP vs D (p = 0.11) (Table). Overall, 11.5% of pts achieved the 1 endpt with no difference between groups (Grp 1 vs Grp 3; Grp 2 vs Grp 3 [p = 0.43; p = 0.75]). T rec was shortest in Grp 1 relative to Grp 3 (p < 0.001). Clinical trial information: NCT01751451. Conclusions: Although no difference between tx grps was identified by the 1 endpt (PSA0 + T rec), these results set a benchmark for future trials that 10‐15% of pts can achieve this outcome. Given the survival benefit of AAP + ADT in non‐castrate met PC, a longer duration of androgen suppression may yield greater benefit. In addition to novel systemic txs, use of PET directed imaging to identify and target micro‐mets with focal txs may enhance the likelihood of eliminating disease in this setting. (Table Presented).