Clinical Trial Data in Metastatic HSPC From the ASCO 2022 Annual Meeting

Transcript:
Evan Y. Yu, MD: Some things from this conference have been brought into the conversation but there's obviously been some other new findings in the hormone sensitive or castration sensitive disease space. Mary-Ellen, do you have any favorite abstracts that you saw here at the meeting that you thought were of interest for this disease state?

Mary-Ellen Taplin, MD: We just mentioned the updated overall survival for the enzamet trial. That was helpful data to have that we know that both enzalutamide and abiraterone from a post-hoc analysis from STAMPEDE has resulted in overall survival for these patients. An important endpoint and when you're talking about trial design per our last comments, what's important for the clinician with the patient in front of them is to understand what the primary endpoints of the study were. That's what the trial was powered to detect and to relay that information accurately to the patient because patients might have reasons to choose doing a treatment or not doing a treatment if they know that they're going to live longer versus their scans might be better for a while longer, but they might not live longer in the end. For us practicing clinicians it's important to primarily understand what the endpoint was. I think that was helpful. Today we heard the update of the overall survival with enzamet and enzalutamide has held up as increasing overall survival. What's remarkable about that is the patients in the control arm all get a lot of subsequent therapy including enzalutamide and abiraterone and despite that, the early use of enzalutamide has allowed these patients to live longer and as Andy said a lot of the patient are continued on drug for many years and that is a remarkable benefit to their life because every time you have to meet with a patient and explain that their disease is progressing and you need to switch to a new therapy, that's a very stressful time for that patient and so this is remarkably great data to have.

Evan Y. Yu, MD: OK great anybody else, did you see anything that you really liked in this disease state that you thought well that's neat I'm going to use that in the clinic?

Andrew J. Armstrong, MD, MSc: Yes, I'd like to put in a plug for one of our posters on Monday in the arches analysis. This was something that we were interested in looking at how patients progress when they're on enzamet ADT and this can be applied to any AR therapy. What we found is that many patients had radiographic progression when on a potent AR inhibitor without PSA progression. We're all kind of used to laying back and not doing imaging very often as you see that PSA go down but what we saw is that about a third of the patients when they had imaging progression at soft tissue or new bone metasis they didn't have any rise in PSA at all and that's kind of a scary thought.

Evan Y. Yu, MD: A third, wow.

Andrew J. Armstrong, MD, MSc: Those patients have a worse survival when that happens so it would emphasize the need for imaging not just to rely solely on PSA when you're monitoring patients’ long term and this would be true for any of the AR inhibitors.

Evan Y. Yu, MD: Do you think that's just more AR, low AR in different disease, neuroendocrine transformation, the mix of everything?

Andrew J. Armstrong, MD, MSc: It could be. You're also suppressing AR because of the enza itself and so the chromatin could remodel, the lineage plasticity could develop among many different factors and PSA may not be a good read out of that anymore.

Transcript edited for clarity.