Dr Bobby Liaw talks about relationship between treatment duration, dosing and efficacy.
Bobby Liaw, MD: Once patients are started on treatment for metastatic castration-sensitive prostate cancer — with the exception of docetaxel which concludes after 6 cycles of treatment — the way that other androgen receptor pathway targeting agents were studied is we would start them and continue them for as long as we find that they are still demonstrating disease control. As long as we're not running into barriers in terms of tolerability due to side effects.
Most patients will stay on 1 of the AR-directed therapies for quite some time depending on which drug you're on. Depending on which study you look at, there'll be varying amounts of time that people are on-study. As an example, from the TITAN study looking at apalutamide, median duration of treatment for patients who received apalutamide was 39 months. But if you look at other studies, such as LATITUDE for abiraterone, the time to next line of therapy was quoted as 54.9 months. It doesn't necessarily mean that they were on the drug the entire time, but that's how much time it took for them to go onto the next line of therapy. Now, it is a significant amount of time that people are on treatment. And certainly, there will be patients that experience side effects. For a lot of patients who may run into difficulties in tolerating, there are a couple of ways for us to get around that, either by interrupting dose by holding treatment, or by dose reduction. Looking at people on study that had treatment discontinuation across the different AR drugs, it's somewhere around 10%, 12% of people. It's harder to fully quantify exactly how many people have those reductions and whether or not they were able to get that back up to full dose. But a common question that patients will ask surrounding any holding doses or dose reductions is, how does this impact my treatment? How does this impact my disease control? To be honest, that's a little bit harder to say, because we don't have a lot of robust clinical trial data here to cite. However, we do know from earlier phase studies that lower doses of drugs, whether it's abiraterone, enzalutamide, or apalutamide, were still associated with a significant antineoplastic effect. But I think in the end, we all have the feeling that a clinical response is most likely optimized at full dosing and full density.
I’m going to refer back to TITAN again, just to use apalutamide as an example, but on that study, 7.1% of patients required a dose reduction, and those patients were still included in the overall analysis. And the overall analysis still shows that we still see a consistent clinical effect from the medication for people on a dose reduction.
Transcript edited for clarity.