Andrew Armstrong, MD, Duke Cancer Institute, Durham, North Carolina, discusses the 5-year follow-up results from the ARCHES trial. This phase 3 trial investigated enzalutamide plus androgen-deprivation therapy (ADT) among patients with metastatic hormone-sensitive prostate cancer.

Previously, the final overall survival analysis from ARCHES demonstrated a significant reduction in the risk of death with enzalutamide and ADT. This 5-year follow-up analysis showed results consistent with previous analyses, a benefit across all subgroups of patients with metastatic hormone-sensitive prostate cancer.

These data were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Transcript: 

Hi, I'm Andrew Armstrong, a medical oncologist at Duke University, and the principal investigator of the ARCHES study, and I presented at ASCO 2025 the 5-year overall survival results from this phase 3 study.

To give some background, ARCHES was a global, randomized, phase 3 study of 1150 men all with metastatic hormone-sensitive prostate cancer, that means prostate cancer that had spread either after local therapy, or these men had presented de novo with metastatic disease. The standard of care at the time we designed ARCHES, more than 8 years ago, was androgen deprivation therapy [ADT]. The field has come a long way since then, largely because of trials like ARCHES, as well as many others, that have shown that treatment intensification with drugs like enzalutamide, which was the experimental agent used in the ARCHES trial, have extended the survival and the progression-free survival in many contexts. 

In 2019, enzalutamide was shown to delay progression-free survival by 60%, that led to the FDA at that time. In 2021, we showed with longer follow up that overall survival was improved by about 30% in ARCHES. The 5-year data is very compelling, what we show is that in high-volume patients’ median survival is extended by 3 additional years of life, going from 4 years of survival with androgen deprivation therapy alone– it's a very poor prognosis, to now 7 years of survival with the combination of enzalutamide plus ADT. Three years of life for my patients is very meaningful, that gives patients more durable quality of life, better disease control, more time with their family and loved ones for making it to important events. The chance of being alive at 5 years went from about 53% to 66%. That means 2/3 of patients are alive at that important landmark, it also means that past 5 years most patients are alive, so it's giving a lot of hope to patients long term. 

With enzalutamide comes the need to manage survivorship. We do see enhanced toxicities related to this very potent androgen receptor pathway inhibition, we do see some muscle loss, fatigue, some frailty, some increased risk of falls and fractures because of that particularly in older men. High blood pressure is another known side effect of many of the androgen receptor pathway inhibitors, including enzalutamide, so it's really important to monitor for high blood pressure, to manage that, to manage cardiovascular risk, to monitor cardiovascular risk, to monitor bone health, to institute a structured exercise program for our patients that's very personalized, individualized to patients who are going through this journey and to take calcium, vitamin D, monitor bone density, and institute bone prophylaxis to reduce the risk of fractures. All this together will help your patients live a lot longer.

On behalf of my ARCHES coauthors, we’re very excited to show that the ARCHES regimen basically extended survival regardless of where you lived in the world, the geography, the Gleason score, the volume of disease, prior docetaxel, all these subgroups benefited and that's what we showed at our presentation. Thank you.

Source:

Armstrong A, Petrylak D, Shore N, et al. ARCHES: 5-year overall survival (OS) analysis of enzalutamide (ENZA) plus androgen-deprivation therapy (ADT) in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC). Presented at the 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract #5005.