Andrew J. Armstrong, MD, MS, on ARCHES: 5-Year Overall Survival Follow-up

So in 2025, the standard of care for men who have metastatic hormone-sensitive prostate cancer is treatment intensification, either with doublet therapy, that means androgen deprivation therapy plus an androgen receptor pathway inhibitor, or triplet therapy with that doublet plus docetaxel. And that's based on data like the ARCHES trial that I'm presenting at ASCO 2025. In 2019, we published in the Journal of Clinical Oncology that enzalutamide plus ADT in the ARCHES trial delayed progression-free survival by over 60%. That led to the FDA approval of the enzalutamide ADT regimen based on the ARCHES trial of over 1,150 patients. This is a randomized global trial, the primary endpoint of which was radiographic progression-free survival. In 2021 we updated the data that shows that that delay in progression-free survival translated into an overall survival improvement by about 30%. So this was a remarkable finding in 2021. In 2025 we're updating the data where the minimum follow-up for all patients is now five years. So we're asking the question what does this long-term survival look like for our patients and this is applicable to clinical practice as we're now treating patients, as I mentioned, in 2025 with treatment intensification routinely. And the question is what happens to these men long-term. The great news from the ARCHES long-term survival follow-up is that men are living longer, a 30% extension of survival. That means at five years 13% more men are alive at that important landmark. This ranges across different subgroups by disease volume, disease risk, geography, age, prior chemotherapy, but the absolute improvement ranges from about 9 to 17%. One of the more remarkable findings was the median survival improvement in high-volume disease patients. Survival improved from four years to about seven years. That's three extra years of life where these men can enjoy time with their family, delay progression and the symptomatology that that causes, delay the need for chemotherapy and subsequent therapy, which have additional toxicities. Now with this improved efficacy and delaying progression and living longer comes the need for close attention to survivorship. There are enhanced toxicities with all of the androgen receptor pathway inhibitors. With enzalutamide we do see increases in fatigue, falls, some fractures, particularly in older men. We see neurocognitive effects in a few percent of patients. Radioligand therapy, EZH2 inhibitors, you know, ways to further build on this and extend the lives of our patients.