Stephen Freedland, MD, Cedar-Sinai Medical Center, Los Angeles, CA, and Durham VA Medical Center, NC, discusses study results exploring real-world evidence on survival outcomes among men with castrattion-resistant prostate cancer who initiated androgen deprivation therapy (ADT) or ADT combined with anti-androgens, docetaxel, or abiraterone.
These results were presented at the virtual 2021 ASCO Genitourinary Cancers Symposium.
Hi, I'm Steve Freedland. I'm a urologist at Cedars‑Sinai Medical Center with a joint appointment at the Durham VA Medical Center in Durham, North Carolina. It's my honor today to talk to you about our study entitled "Survival Outcomes in Patients with Metastatic Castrate‑Sensitive Prostate Cancer (mCSPC): A Real‑World Evidence Study."
I am presenting on behalf of myself and my co‑authors, and this study was funded by both Pfizer and Astellas, and both myself as well as the co‑authors are either employees of Astellas and/or Pfizer, or have consulting agreements and collaborate with them.
One of the questions we wanted to look at was we know in metastatic castrate‑sensitive disease that, for decades, androgen deprivation therapy, ADT, has been the standard of care. We now know, newer data suggests, if we add additional agents, whether it be enzalutamide, apalutamide, abiraterone, or docetaxel, we can get a survival benefit.
The question is, how well is that information permeating into clinical practice?
The second question we wanted to ask is, we know a lot of men are still getting ADT plus anti‑androgens, the old‑fashioned combined androgen blockage. We wanted to understand how that practice pattern has changed over time, as well as to see if there are any differences in progression and survival rates between men on ADT versus those on ADT plus anti‑androgens.
To do this, we used data from the VA health system. It's the largest integrated health system in the country and allows us pretty large numbers to look at things. Once we did that and actually started playing with the analyses and actually looking at those who had metastatic castrate‑sensitive disease—this is a claims‑based analysis using VA data.
They had to have a code for metastases. They needed to have started hormonal therapy. They couldn't have been mCRPC—castrate resistant. We did all that. At the end of the day, we ended up with about 1400 men.
If we look at those men, what you would see is, as you would expect from a prostate cancer patient population, they tended to be older men. Mean age was in the early 70s. One of the nice things about using VA data is we actually had a large representation of black men.
We had over 25%, almost 30%, of the entire cohort was black. If we look down, in terms of some of the key findings that we saw in the study, was first off that, if we went back to an era before CHAARTED, before we knew docetaxel and the AR‑targeted therapies had a benefit, you saw that about 97% of the men were getting either ADT alone, which was two-thirds of men, or ADT plus anti‑androgens.
That was clearly the dominant practice, and that made sense. That's the data we knew.
What's been a little disappointing, I would say—but I think represents real‑world practice, and we've seen this outside the VA—is that, even as we moved onto 2017 to early 2018, where we now had CHAARTED, you had LATITUDE, you had the STAMPEDE, you had multiple studies suggesting the benefits, you still saw 60% of the men were getting ADT alone.
Another 17% were getting ADT plus anti‑androgens. The use of novel hormonal agents was only 15% of patients, and docetaxel, which actually peaked in 2016, was down to 9% of patients. Less than a quarter of patients during that era.
Again, we're going to 2017, so this is pre‑ENZAMET, pre‑ARCHES, pre‑TITAN, so the data wasn't quite as robust, but we certainly knew that those agents had benefits, abiraterone and docetaxel. That's what we looked at, was abiraterone and docetaxel. It was still less than a quarter of patients were getting that.
That was one of the key findings that we had of the study. The second was we actually looked at outcomes. What is the risk of a patient going on and to develop castrate resistances, and then ultimately, overall survival?
What we saw is, if you looked at the time to progression, what we saw is that there was no difference between ADT and ADT plus an anti‑androgen, the combined androgen blockade, but survival was slightly worse with the ADT plus anti‑androgen group.
Which on the one hand, doesn't necessarily intuitively make sense. On the other hand is, when you actually look at it, the men who got the ADT plus anti‑androgens had more aggressive disease.
Intuitively, the doctor saw the patient. They had more advanced disease, higher PSAs, more visceral mets and things, and the doctor said, "Wow, this is bad disease. I'm going to give them ADT plus an anti‑androgen." You need to adjust for some of those baseline differences.
When we did that, then we saw absolutely no difference in time to mCRPC and no difference in overall survival. Basically, saying we could explain the worse outcomes by adjustment for patient characteristics.
Unfortunately, we didn't have enough men starting abiraterone or docetaxel with their ADT to do those kinds of statistics. What's interesting is we look at it historically, there is this idea of this combined androgen blockade, which does suggest a little bit of survival benefit, relative to ADT alone.
It's pretty modest and historical data, but what we're seeing in our real‑world studies, we don't see that benefit. Now, whether that's due to a true lack of benefit or the fact that there was residual confounding, we didn't completely account for all the badness of their disease, or there's truly no difference in the era where we have effective mCRPC therapies.
We have very potent mechanisms to inhibit androgen receptor signaling in the mCRPC, which they didn't in those early meta‑analysis, suggesting a small benefit to combined androgen blockade. Ultimately, again, what we're seeing in the real world is a practice pattern that is still favoring ADT and the ADT plus anti‑androgens.
The use of novel therapies for mCSPC is going up, but it's still relatively modest, albeit 2017, 2018 data, and really no benefit to adding the anti‑androgens. We're very curious to see what an updated dataset will look like and how practice patterns are continuing to change over time.
Thank very much for your attention.
Freedland SJ, Sandin R, Sah J. Survival outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC): A real-world evidence study. Presented at: the virtual 2021 ASCO Genitourinary Cancers Symposium; February 11-13, 2021. Abstract 46.
Dr Freedland reports consultation payment from Astellas; Pfizer; Janssen; Clovis; Merck; AstraZeneca; Sanofi; Bayer; and Myovant is a speaker for AstraZeneca and Sanofi.