Metastatic Hormone-Sensitive Prostate Cancer: Data From ENZAMET and ARCHES

Transcript:

Alan Bryce, MD: Dr Zhang, let's move through the other MHSPC [metastatic hormone-sensitive prostate cancer] studies. Could you speak to the enzalutamide studies. For that we have 2, right? We have ARCHES and ENZAMET. What did those studies teach us?

Tian Zhang, MD, MHS: We were lucky to participate in ARCHES. I know when it was enrolling, I had patients on it. It was a trial in the metastatic hormone sensitive space, as well as in the postdocetaxel space, so it allowed people who had received prior docetaxel on, and it randomized enzalutamide with androgen deprivation therapy or placebo with androgen deprivation therapy. Across groups, we saw an improvement in time until progression and in overall survival. There was an update analysis presented about a year ago, in 2022, that these survival outcomes were preserved across groups irrespective of their disease volume, or whether they had de novo metastatic disease or had prior localized treatment and then progressed to metastatic disease. There were some cohorts that were small subsets. The hazard ratios across subgroups were all ranging from 0.6 to 0.7, and I think across these groups enzalutamide has benefit. ENZAMET was an interesting study that was similarly timed. It was mostly enrolled in the Australian and New Zealand populations. This was also a study where enzalutamide was compared against placebo along with androgen deprivation therapy. Interestingly, there was a cohort of patients who were allowed to receive docetaxel concurring with their enzalutamide. There was an update analysis of overall survival presented about a year ago now—I understand the publication is in press—and that looked at these subsets of patients. Were they synchronous, high-volume disease? synchronous, low-volume disease? Or did they have metachronous metastatic disease with low or high volume? In asking that docetaxel question, we saw that enzalutamide predominantly was effective across these subgroups. It's interesting that the patients who received docetaxel along with their enzalutamide had more of an early benefit. In our house, we call these high-volume synchronous metastases, a series of clone wars, right? There are multiple clones at play, and who needs docetaxel? The people who have a lot of disease, a lot of clones and some may not be so sensitive to our androgen receptor targeted therapies. Those are the right patients in my mind that might benefit from docetaxel. I think that's why we see the skirting of the curves early on for docetaxel treated patients in the synchronous high-volume disease.

Alan Bryce, MD: It's a great point. We're all putting a lot of effort into these ideas around clonality. How do we hit these different populations? We know docetaxel is an effective drug, but we want to figure out the best way to use it. That's where we're at.

Transcript edited for clarity.