Bipolar Androgen Therapy vs Enzalutamide in Asymptomatic Men With Castration-Resistant Metastatic Prostate Cancer.

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In this prospective phase II study, men with metastatic castration-resistant prostate cancer (mCRPC) previously treated with abiraterone were randomized to receive bipolar androgen therapy (BAT) or enzalutamide (enza). Crossover was permitted. With a PSA response of approximately 28%, BAT showed clinically significant activity compared with enza and was associated with the same progression-free survival (PFS) and numerically longer PSA PFS and overall survival. Furthermore, the sequence BAT-enza was associated with significantly longer PFS2 compared with the opposite sequence (28.2 vs 19.6 months).

BAT-enza may be an effective therapy for patients with mCRPC with progression on abiraterone. Further research is required for optimal clinical use and to identify biomarkers to predict treatment efficacy.

– Emily Miller, MD

Abstract

This abstract is available on the publisher's site.

PURPOSE

Prostate cancer (PCa) becomes resistant to androgen ablation through adaptive upregulation of the androgen receptor in response to the low-testosterone microenvironment. Bipolar androgen therapy (BAT), defined as rapid cycling between high and low serum testosterone, disrupts this adaptive regulation in castration-resistant PCa (CRPC).

METHODS

The TRANSFORMER (Testosterone Revival Abolishes Negative Symptoms, Fosters Objective Response and Modulates Enzalutamide Resistance) study is a randomized study comparing monthly BAT (n = 94) with enzalutamide (n = 101). The primary end point was clinical or radiographic progression-free survival (PFS); crossover was permitted at progression. Secondary end points included overall survival (OS), prostate-specific antigen (PSA) and objective response rates, PFS from randomization through crossover (PFS2), safety, and quality of life (QoL).

RESULTS

The PFS was 5.7 months for both arms (hazard ratio [HR], 1.14; 95% CI, 0.83 to 1.55; P = .42). For BAT, 50% decline in PSA (PSA50) was 28.2% of patients versus 25.3% for enzalutamide. At crossover, PSA50 response occurred in 77.8% of patients crossing to enzalutamide and 23.4% to BAT. The PSA-PFS for enzalutamide increased from 3.8 months after abiraterone to 10.9 months after BAT. The PFS2 for BAT→enzalutamide was 28.2 versus 19.6 months for enzalutamide→BAT (HR, 0.44; 95% CI, 0.22 to 0.88; P = .02). OS was 32.9 months for BAT versus 29.0 months for enzalutamide (HR, 0.95; 95% CI, 0.66 to 1.39; P = .80). OS was 37.1 months for patients crossing from BAT to enzalutamide versus 30.2 months for the opposite sequence (HR, 0.68; 95% CI, 0.36 to 1.28; P = .225). BAT adverse events were primarily grade 1-2. Patient-reported QoL consistently favored BAT.

CONCLUSION

This randomized trial establishes meaningful clinical activity and safety of BAT and supports additional study to determine its optimal clinical integration. BAT can sensitize CRPC to subsequent antiandrogen therapy. Further study is required to confirm whether sequential therapy with BAT and enzalutamide can improve survival in men with CRPC.

Citation: Journal of Clinical Oncology

TRANSFORMER: A Randomized Phase II Study Comparing Bipolar Androgen Therapy Versus Enzalutamide in Asymptomatic Men With Castration-Resistant Metastatic Prostate Cancer

J. Clin. Oncol 2021 Feb 22;[EPub Ahead of Print], SR Denmeade, H Wang, N Agarwal, DC Smith, MT Schweizer, MN Stein, V Assikis, PW Twardowski, TW Flaig, RZ Szmulewitz, JM Holzbeierlein, RJ Hauke, G Sonpavde, JA Garcia, A Hussain, O Sartor, S Mao, H Cao, W Fu, T Wang, R Abdallah, SJ Lim, V Bolejack, CJ Paller, MA Carducci, MC Markowski, MA Eisenberger, ES Antonarakis

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

[Cooolone]

Study link?

[Rilu]

Very very useful, thanks!!! The link: ascopubs.org/doi/10.1200/JC...