Longer Duration of Androgen Suppression Examined in Phase 2 Study

Chicago—Androgen signaling is not entirely suppressed with androgen deprivation therapy (ADT) with GnRH analogs. Abiraterone acetate plus prednisone added to ADT decreases blood and intramural levels of testosterone by ≥1 log, and, in pre-radical prostatectomy trials, resulted in greater pathologic responses compared with ADT alone.

Given the long history of prostate cancer and the resources required for phase 3 trials, study designs that aim to rapidly assess therapies are critical, according to Karen A. Autio, MD, and colleagues who used a novel end point (undetectable prostate-specific antigen [PSA] with testosterone recovery) to test the hypothesis that abiraterone acetate in combination with prednisone administered in the “rising PSA state following radical prostatectomy, a low volume but potentially lethal setting, could eliminate all disease, a prerequisite to cure.”

The researchers reported results of the study during a poster session at the ASCO 2018 Annual Meeting in a poster titled 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).

Patients who underwent radical prostatectomy ± salvage radiotherapy with a rising PSA ≥1.0 ng/mL, PSA doubling time ≤9 months, no metastases on computed tomography/bone scan, and testosterone ≥150 ng/mL were eligible to participate in the study. Prior ADT ≤8 months was allowed.

Patients were randomized in a 1:1 ratio to receive 1000 mg abiraterone acetate plus 5 mg prednisone once daily (group 1) abiraterone acetate plus prednisone plus monthly degarelix (group 2), or monthly degarelix (group 3) for 8 months, followed by cessation of therapy. The primary end point of interest was PSA0 with testosterone >150 at 18 months; a secondary end point was PSA0 at 8 months.

A total of 120 patients were treated. Of those, 113 were evaluable for the primary end point; seven had PSA0 at 18 months without testosterone recovery. At 8 months, there was no difference in PSA0 in group 1 compared with group 2 or group 3. Overall, 11.5% of patients achieved the primary end point with no difference between groups. Testosterone recovery was shortest in group 1 compared with group 3.

In summary, the researchers said, “Although no difference between treatment groups was identified by the primary end point (PSA0 + testosterone recovery), these results set a benchmark for future trials that 10-15% of patients can achieve this outcome. Given the survival benefit of abiraterone acetate plus prednisone in non-castrate metastatic prostate cancer, a longer duration of androgen suppression may yield greater benefit. In addition to novel systemic therapies, use of positive emission tomography directed imaging to identify and target micro-mets with focal therapies may enhance the likelihood of eliminating disease in this setting.”

Clinical trial information: NCT01751451

Source: Autio KA, Antonarakis ES, Mayer TM, et al. Phase 2, randomized, 3-arm study of abiraterone acetate and prednisone (AAP), AAP plus degarelix (AAP + P), and degarelix (D) alone for patients (pts) with biochemically recurrent prostate cancer (PC) following radical prostatectomy (RP). Abstract of a poster presented at the American Society of Clinical Oncology 2018 Annual Meeting, June 2, 2018, Chicago, Illinois.