Hormone Therapy (ADT) is the standard of care for prostate cancer. ADT is practiced by either halting the production of androgens or blocking them from interacting with the hormone receptor, so the cancer cells cannot utilize the androgens.
This method of ADT usually results in the development of resistance where the therapy stops working and the cancer continues to progress.
There has been discussion and some recent evaluation of an alternative type of hormone therapy (Bipolar Androgen Therapy or BAT). Instead of removing androgens, the treatment floods the cancer cells with androgens. It then quickly halts the exposure of the cells to androgens. The key to BAT is that there is rapid cycling back and forth from high levels of androgen exposure to the deprivation of androgens.
One of the most recent trials evaluating BAT was the TRANSFORMER trial.
TRANSFORMER was a phase 2 trial (ClinicalTrials.gov Identifier: NCT02286921) that randomly assigned 195 asymptomatic men with metastatic castrate resistant prostate cancer (mCRPC). The men received either monthly BAT using testosterone cypionate and then enzalutamide or just enzalutamide. The primary endpoint was progression free survival (PFS), and secondary endpoints included overall survival (OS), PSA, and safety. Crossover, going from one group to the other, was allowed at progression.
TRANSFORMER found that BAT resulted in similar progression-free survival and reduction in prostate-specific antigen (PSA) compared with enzalutamide alone, according to the results published in the Journal of Clinical Oncology.
The study also showed that the median OS was also not significantly different, with a median of 32.9 months with BAT compared with 29.0 months with enzalutamide (HR, 0.95; 95% CI, 0.66-1.39; P =.80).
In a subgroup analyses of the data, both PFS and OS favored BAT among men who had a short-term response (defined as less than 6 months) to abiraterone.
Crossover occurred primarily as a result of radiographic progression. The median OS among the men who crossed over to enzalutamide alone was 37.1 months compared with 30.2 months among men who crossed over to BAT (HR, 0.68; 95% CI, 0.36-1.28; P =.23).
“The TRANSFORMER trial is unique in that it compares two treatments with diametrically opposite effects on the androgen receptor therapeutic target,” the authors wrote.
The authors concluded that “TRANSFORMER establishes meaningful clinical activity of BAT and supports additional study to determine its optimal clinical integration.”
Reference
Denmeade SR, Wang H, Agarwal N, et al. TRANSFORMER: A randomized phase II study comparing bipolar androgen therapy versus enzalutamide in asymptomatic men with castration-resistant metastatic prostate cancer. J Clin Oncol. Published online February 22, 2021. doi:10.1200/JCO.20.02759
