Randomized Phase 2 Trial of Abiraterone Acetate Plus Prednisone, Degarelix, or the Combination in Men with Biochemically Recurrent Prostate Cancer After Radical Prostatectomy

Karen A Autio; Emmanuel S Antonarakis; Tina M Mayer; Daniel H Shevrin; Mark N Stein; Ulka N Vaishampayan; Michael J Morris; Susan F Slovin; Elisabeth I Heath; Scott T Tagawa; Dana E Rathkopf; Matthew I Milowsky; Michael R Harrison; Tomasz M Beer; Arjun V Balar; Andrew J Armstrong; Daniel J George; Channing J Paller; Arlyn Apollo; Daniel C Danila; Julie N Graff; Luke Nordquist; Erica S Dayan Cohn; Kin Tse; Nicole A Schreiber; Glenn Heller; Howard I Scher

doi:10.1016/j.euros.2021.09.015

Randomized Phase 2 Trial of Abiraterone Acetate Plus Prednisone, Degarelix, or the Combination in Men with Biochemically Recurrent Prostate Cancer After Radical Prostatectomy

Eur Urol Open Sci. 2021 Nov 17:34:70-78. doi: 10.1016/j.euros.2021.09.015. eCollection 2021 Dec.

Authors

Karen A Autio^{1

2}, Emmanuel S Antonarakis³, Tina M Mayer⁴, Daniel H Shevrin⁵, Mark N Stein⁶, Ulka N Vaishampayan⁷, Michael J Morris^{1

2}, Susan F Slovin^{1

2}, Elisabeth I Heath⁸, Scott T Tagawa², Dana E Rathkopf^{1

2}, Matthew I Milowsky⁹, Michael R Harrison¹⁰, Tomasz M Beer¹¹, Arjun V Balar¹², Andrew J Armstrong¹⁰, Daniel J George¹⁰, Channing J Paller¹³, Arlyn Apollo¹, Daniel C Danila¹, Julie N Graff¹¹, Luke Nordquist¹⁴, Erica S Dayan Cohn¹, Kin Tse¹⁵, Nicole A Schreiber¹⁶, Glenn Heller¹⁷, Howard I Scher^{1

2

18}

Affiliations

¹ Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
² Weill Cornell Medical College, New York, NY, USA.
³ University of Minnesota Medical School, Minneapolis, MN, USA.
⁴ Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
⁵ NorthShore University HealthSystem, Evanston, IL, USA.
⁶ Columbia University Herbert Irving Comprehensive Cancer Center, New York, NY, USA.
⁷ University of Michigan, Ann Arbor, MI, USA.
⁸ Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
⁹ UNC Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
¹⁰ Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA.
¹¹ Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
¹² New York University, New York, NY, USA.
¹³ Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, Baltimore, MD, USA.
¹⁴ Urology Cancer Center and GU Research Network, Omaha, NE, USA.
¹⁵ Columbia University, New York, NY, USA.
¹⁶ Convergent Therapeutics, New York, NY, USA.
¹⁷ Biostatistics Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁸ Prostate Cancer Clinical Trials Consortium, New York, NY, USA.

Abstract

Background: Phase 2 trial endpoints that can be utilized in high-risk biochemical recurrence (BCR) after prostatectomy as a way of more rapidly identifying treatments for phase 3 trials are urgently needed. The efficacy of abiraterone acetate plus prednisone (AAP) in BCR is unknown.

Objective: To compare the rates of complete biochemical responses after testosterone recovery after 8 mo of AAP and degarelix, a gonadotropin-releasing hormone antagonist, alone or in combination.

Design setting and participants: Patients with BCR (prostate-specific antigen [PSA] ≥1.0 ng/ml, PSA doubling time ≤9 mo, no metastases on standard imaging, and testosterone ≥150 ng/dl) after prostatectomy (with or without prior radiotherapy) were included in this study.

Intervention: Patients were randomized to AAP (arm 1), AAP with degarelix (arm 2), or degarelix (arm 3) for 8 mo, and monitored for 18 mo.

Outcome measurements and statistical analysis: The primary endpoint was undetectable PSA with testosterone >150 ng/dl at 18 mo. Secondary endpoints were undetectable PSA at 8 mo and time to testosterone recovery.

Results and limitations: For the 122 patients enrolled, no difference was found between treatments for the primary endpoint (arm 1: 5.1% [95% confidence interval {CI}: 1-17%], arm 2: 17.1% [95% CI: 7-32%], arm 3: 11.9% [95% CI: 4-26%]; arm 1 vs 2, p = 0.93; arm 2 vs 3, p = 0.36). AAP therapy showed the shortest median time to testosterone recovery (36.0 wk [95% CI: 35.9-36.1]) relative to degarelix (52.9 wk [95% CI: 49.0-56.0], p < 0.001). Rates of undetectable PSA at 8 mo differed between AAP with degarelix and degarelix alone (p = 0.04), but not between AAP alone and degarelix alone (p = 0.12). Limitations of this study include a lack of long-term follow-up.

Conclusions: Rates of undetectable PSA levels with testosterone recovery were similar between arms, suggesting that increased androgen suppression with AAP and androgen deprivation therapy (ADT) is unlikely to eradicate recurrent disease compared with ADT alone.

Patient summary: We evaluated the use of abiraterone acetate plus prednisone (AAP) and androgen deprivation therapy (ADT), AAP alone, or ADT alone in men with biochemically recurrent, nonmetastatic prostate cancer. While more men who received the combination had an undetectable prostate-specific antigen (PSA) level at 8 mo on treatment, once men came off treatment and testosterone level rose, there was no difference in the rates of undetectable PSA levels. This suggests that the combination is not able to eradicate disease any better than ADT alone.

Keywords: Abiraterone; Androgen; Androgen deprivation therapy; Biochemical recurrence; Degarelix; Prostate cancer; Prostate-specific antigen.

Grants and funding

P30 CA008748/CA/NCI NIH HHS/United States