Estradiol patches noninferior to LHRH agonists in locally advanced prostate cancer

Abstract

Transdermal estradiol (tE2) patches were noninferior to luteinizing hormone–releasing hormone (LHRH) agonists as a form of androgen deprivation therapy (ADT) in patients with locally advanced prostate cancer according to a study published in The New England Journal of Medicine.¹

Ruth E. Langley, FRCP, PhD, professor of oncology and clinical trials at University College London in the United Kingdom, and her colleagues conducted a phase 3 noninferiority trial comparing 3-year metastasis-free survival in 1360 patients with locally advanced prostate cancer who were randomly assigned to receive tE2 patches or LHRH agonists. Patients were recruited through the PATCH or STAMPEDE-1 trial networks.

“In prostate cancer, lowering testosterone is a key part of treatment; for the last 30-40 years, that has been done mainly with LHRH agonists,” says Dr Langley. “When you do this, you get two types of side effects, those from low testosterone and those from low estrogen, which causes symptoms like weakened bones and hot flashes.”

Previous research into tE2 patches showed that their use did not increase cardiovascular risk and improved quality of life and preservation of bone mineral density in comparison with LHRH agonists, Dr Langley says. With this phase 3 study, Dr Langley and her colleagues wanted to specifically evaluate prostate cancer outcomes and see if similar outcomes could be achieved with fewer side effects with tE2 versus LHRH agonists.

The observed 3-year metastasis-free survival rate was noninferior with tE2 at 87.1% versus 85.9% with LHRH agonists (hazard ratio [HR] for confirmed metastasis or death, 0.96). The observed 5-year overall survival rates were also similar: 81.1% with tE2 and 79.2% with LHRH agonists (HR for death, 0.90).

The side-effect profile for each treatment approach varied. Among patients assigned to tE2 only, 44% experienced hot flashes, whereas 89% of patients assigned to LHRH agonists did. In contrast, gynecomastia occurred in 85% of patients assigned to tE2 versus 42% of patients assigned to LHRH agonists.

“I interpret these data to say that tE2 patches could theoretically be used in lieu of LHRH agonists for people with nonmetastatic hormone-sensitive prostate cancer as long as there is an understanding of the risks and the benefits,” says Rana R. McKay, MD, a medical oncologist and professor of medicine and urology at the University of California, San Diego.

“Another thing for patients to consider, but this wasn’t quantified in this trial, is that tE2 therapy could potentially have a protective bone effect,” Dr McKay mentions.

Dr Langley agrees that choosing between these two therapies will be very personal. “Younger men who are going to the gym every day, as an example, may be more concerned with their physical appearance and will not want gynecomastia,” Dr Langley says. “But some men who have experienced the hot flashes and disturbed sleep are becoming exhausted and may want a change.”

Having these two options will require a much more open discussion about patients’ goals when they are starting ADT, says Dr Langley. Overall, having these options reflects progress.

“If you go back 20 years when prostate cancer outcomes were not so good, there was less consideration about what a patient’s bone health would be in 15 years,” Dr Langley says. “Now, because outcomes are improved, these discussions are very relevant for our patients.”