Long-Term Data with Androgen Receptor Pathway Inhibitors


A prostate cancer expert shares long-term data with androgen receptor pathway inhibitors in mCSPC.

Atish Choudhury, MD, PhD: So, the question is, what is the long-term data in terms of overall survival from TITAN which was a study of apalutamide, and ARCHES, which is a study of enzalutamide, and how does that compare to previous data? I would say that that data basically confirms findings from previous studies, including LATITUDE of abiraterone, STAMPEDE of abiraterone, and ENZAMET of enzalutamide that all really demonstrate prolongation of overall survival when adding an AR pathway inhibitor to initial ADT.

So, it’s not clear from those studies that any of the agents is superior to any of the other agents in terms of the overall survival. I think we can only include--conclude that they’re all superior to ADT alone. So, that brings us to a question then, well, if the survival is better than what are the barriers to treating patients with these agents, and why are so many patients getting ADT alone in this setting? I think that some of this is a little bit of a misunderstanding of what that overall survival means.

So, the patients on these studies were randomized to get these AR pathway inhibitors with ADT compared to ADT alone, but patients who got ADT alone could get these AR pathway inhibitors at the time of progression. And so it’s clear that earlier treatment with these agents prolongs overall survival. So, there’s a question about, well, if we introduce these agents earlier, is that going to cause earlier onset of resistance, and then we have less agents at the time of progression?

However, if the earlier onset of resistance was problematic in terms of cancer control, then that would play out as a decrease in overall survival. Similarly, questions about side effect profile. Are these agents leading to earlier mortality? And again, if there was toxicity that was leading to overall--to worsened mortality, then you would see that in overall survival as well. Then there’s another question about quality of life, and it’s clear that these agents improve quality of life for these patients over time.

Even though there are side effects to these treatments, they clearly decrease the adverse effects associated with the cancer itself, and so the quality of life with these agents is superior than for patients who are treated with ADT alone. So, there’s not really either a cancer-related or quality of life reason to not consider these agents earlier in the process.Another consideration, obviously, is cost, and cost is absolutely a meaningful consideration in many of these patients.

One thing to consider is that most of these agents are covered well by insurance, and so the variability is really around copays, and most of the manufacturers do have copay assistance. Certainly abiraterone is a lower-cost option, and now that it’s generic, and there is alternative dosing schedule of abiraterone using one pill a day rather than four pills a day that can be used if one is in a pinch and there really aren’t really good assistance options for the other medications.

So, again, unless a patient has really severe contraindications to these agents, it’s clear from all of the studies that overall survival and quality of life is benefitted by the earlier use, and so we would advocate it in really almost all patients in this setting.

Transcript edited for clarity.

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