Dr Liaw discusses ways to measure response to treatment and what recent data regarding PSA kinetics has shown.
Bobby Liaw, MD: We generally evaluate efficacy of our prostate cancer treatment in three ways: symptoms, PSA [prostate-specific antigen tests], and imaging. I usually repeat this to my patients every now and then, to remind them that a lot of the conversations that we have during our visit isn't really just idle banter. It's really designed to probe for symptoms that might give me concern that something's going on with their prostate cancer, or to hopefully see if the clinical symptoms stemming from the disease are starting to improve on treatment. And of course, it's to figure out if there's any side effects that we need to pick up on. But PSA remains a humongous subject in the defining of efficacy. It has been and remains a very important biomarker for us to file for prostate cancer.
While we don't have quite as many studies these days that use percent PSA decline as a major endpoint, I still feel PSA kinetic provides us with a lot of valuable clinical data. There were actually a couple of recent abstracts at the AUA [American Urological Association] meeting as well as at GU ASCO [ASCO Genitourinary Cancers Symposium] over this year that tries to look a little bit at the depth of PSA decline, PSA nadir, and PSA response. There was a really nice abstract that was looking at PSA nadir and the portion of patients achieving a PSA decline of greater than 90% with apalutamide. This analysis was focusing on the patients that participated in the TITAN and SPARTAN studies. The study actually showed that the combination of apalutamide with ADT [androgen deprivation therapy] was associated with high rate of PSA declines of greater than 90% or more at both the 3-month and the 12-month time points. In fact, there were actually greater than 90% declines at the 12-month time point than at the 3-month time point. It was actually a 71% for the TITAN study at 12-months and 61% at 12 months for the SPARTAN study. This really just shows that PSA continues to decline over time. It also showed that the medium time to PSA nadir was about 5.5 months for the TITAN patients and 7.36 months for the SPARTAN patients. Now, I think some of this is important to keep in mind because PSA response and kinetics are important in that it does provide us with some measure of prognostic data on our patients.
I'll talk about a paper that was published back in 2006, by Hussain et al where they found that PSA nadir in patients with metastatic prostate cancer was a strong predictor of survival. In that particular study, it was a study of 1,000-plus patients with newly diagnosed metastatic prostate cancers that had received ADT for 7 months. What it showed was that a PSA nadir to less than 0.2, that group of patients had a median survival of 75-months; compared to those that had a nadir to the range of 0.2 to 4.0, those had a median survival of 44 months. Again, compared with those, that nadir had greater than 4 for PSA; they had a median survival of only 13 months.
You can start to see how PSA nadir really does start to give us a lot of information on how these people will do long term. Now, this particular study by Hussain et al, this was done with just ADT alone. We don't have quite the same level of definitive data in the context of use of combination AR pathway directed inhibitors the way that is permeated or standard of care at this day and age, but there's still a lot of data that's starting to come out to suggest that percent PSA decline and PSA nadir still holds on to some of that prognostic value.
Transcript edited for clarity.