Longer Duration of Androgen Suppression Examined in Phase 2 Study

By DocWire News Editors - Last Updated: May 29, 2018

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.

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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.

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