Estrogen‑Based Androgen Suppression Plus ARSI in Prostate Cancer: A Phase 2 Quality‑of‑Life Trial

A new phase 2 EQUIP trial is comparing two different ways of delivering androgen‑suppressive hormone therapy in men with newly diagnosed or recurrent metastatic hormone‑sensitive prostate cancer, focusing on whether transdermal estrogen patches can improve quality of life compared with standard luteinizing hormone‑releasing hormone (LHRH) analogues. The study is designed around two randomized cohorts, each receiving an androgen receptor signaling inhibitor (ARSI) but differing in how androgen suppression is achieved. In one arm, men receive standard LHRH‑based androgen deprivation therapy; in the other, that LHRH backbone is replaced by transdermal estrogen, with the goal of maintaining good disease control while alleviating the side effects that commonly arise when sex hormones are suppressed.

The trial’s premise is that conventional prostate‑cancer hormone therapy drastically lowers not only androgens but also estrogen, which contributes to troublesome symptoms such as hot flashes, fatigue, impaired bone health, and metabolic and cardiovascular strain. Androgen receptor signaling inhibitors work by blocking the effects of androgen on tumor cells, helping to slow disease progression, while LHRH analogues are a standard form of androgen deprivation that suppresses testosterone production at the pituitary level. The investigators hypothesize that restoring estrogen signaling through transdermal patches, while still using ARSIs to block androgen‑driven tumor growth, may preserve antitumor efficacy while improving well‑being and reducing estrogen‑deficiency–related symptoms.

Patients in this study are randomized to one of two cohorts. In Cohort 1, men receive standard‑of‑care LHRH agonist or antagonist therapy at the approved dose and schedule, continued as long as there is no disease progression or unacceptable toxicity. Four weeks after starting the LHRH agent, patients also begin an ARSI chosen by the treating physician, for at least 12 weeks under the same safety and progression criteria. Men whose daily hot flash score remains at or above 6 after 12 weeks of this standard regimen may be eligible to cross over into the experimental cohort, allowing the trial to capture how symptom‑refractory patients respond when estrogen is introduced.

In Cohort 2, the LHRH‑based androgen deprivation is replaced by estrogen given via transdermal patch on days 1, 4, 8, 12, 16, 20, 24, and 28 of each 28‑day cycle, with cycles repeating in the absence of disease progression or unacceptable toxicity. This estrogen‑patch regimen effectively serves as the primary androgen‑suppressive backbone. Starting four weeks after the patch is initiated, patients also receive an ARSI per physician’s choice for a minimum of 12 weeks, again as long as there is no disease progression or unacceptable toxicity. Across both cohorts, patients undergo CT or MRI, bone scan, DEXA scan, and serial blood sample collection throughout the study to monitor disease control, bone health, metabolic parameters, and treatment safety.

Clinical trial.