New Indications for AR-Targeted Therapy on Prostate Cancer: Including ESMO 2019 Highlights - Episode 9
Transcript: Matthew R. Smith, MD, PhD: The results of 2 recently reported studies provide evidence that enzalutamide is also active in men with metastatic castration-sensitive prostate cancer. In the global phase III ARCHES study, enzalutamide improved progression-free survival compared with placebo, but with short follow-up there was not yet an improvement in overall survival observed.
In a second study of enzalutamide in this disease state called ENZAMET, enzalutamide improved progression-free survival and overall survival compared with placebo. That study was primarily conducted in Australia. Taken together, they provide good support that enzalutamide is also effective in men with metastatic castration-sensitive prostate cancer.
Elizabeth Heath, MD: The ARCHES trial was looking at enzalutamide versus placebo in your castration-sensitive metastatic patients. What’s important about this trial is that it was designed with no worries about disease burden. We’ve spent a lot of time looking at castration-sensitive patients and wondering whether disease burden matters—if you have little minimal disease, you really don’t need much other than androgen deprivation therapy [ADT]. But I think that when you look at the ARCHES trial, it actually looks at whether low burden and high burden matter. And then another subgroup is those who have received docetaxel.
We love to combine things in oncology. For those who have had a set amount of docetaxel in this group, the question was, in addition to androgen deprivation, should we add an androgen receptor modulator? I think 1 of the studies had looked at that, but ARCHES looked at it in a sequential fashion. You’ve had this, and about 15% of people had at least 6 cycles of docetaxel. Does adding enzalutamide help? The answer is yes. I think the overall take-home for ARCHES is that having an androgen receptor modulator—whether you’ve had docetaxel or not, whether you have high-burden disease or not—is still helpful and can prolong your radiological progression-free survival. I think the overall survival will come in time, but it is still an important way to rethink how we treat patients in this space.
Alicia Morgans, MD, MPH: There’s strong evidence for the use of enzalutamide in metastatic castration-sensitive prostate cancer, and this comes from 2 phase III trials. The strongest evidence, and the 1 that should really drive our decision making at this point because of the overall survival advantage that was demonstrated, is the ENZAMET trial. This trial was performed as a phase III international multi-institutional trial. It was led by a cooperative group called the ANZUP [Australia and New Zealand Urogenital and Prostate Cancer Trial Group]. And so it is a very nice example too, of an academic collaboration that can lead to potential approval of a drug.
But this trial randomized patients with metastatic castration-sensitive disease to treatment with ADT plus enzalutamide or ADT plus nilutamide, flutamide, or bicalutamide. These patients also could receive docetaxel chemotherapy, as was the standard of care at that time, concurrent with their treatment. About 45% of patients did receive docetaxel as well as the other treatments. The trial demonstrated that the addition of enzalutamide to ADT was associated with an overall survival benefit as compared with ADT plus nilutamide, flutamide, or bicalutamide. This, again, is an overall survival benefit, so this is our strongest evidence for use of enzalutamide in the patient population.
The ARCHES trial was a phase III multi-institutional international trial as well, but this trial randomized patients with metastatic castration-sensitive disease to treatment with ADT plus enzalutamide or ADT plus placebo. In this trial, they found that there was a radiographic progression-free survival benefit associated with enzalutamide plus ADT. And this was their primary end point, so it’s been reported. Because it’s not overall survival benefit, these data are not as strong for the use of enzalutamide in this patient population. Between the 2 of them, there’s quite strong evidence for the benefit of enzalutamide in metastatic castration-sensitive prostate cancer.
Transcript Edited for Clarity