GU Cancers 2021 | Real-world practice & outcomes in mCSPC

In a collaborative type of a study, including some sponsorship from Pfizer, Steve Freedland and I were able to gain access to a database from the US Veterans Health Administration, the claims-based database. And we started off with nearly 370,000 patients with prostate cancer. And we wanted to be as certain as possible that these patients met our inclusion criteria of initial systemic treatment of metastatic castration-sensitive or i.e. non-castrate metastatic disease. So, of those 370,000, we wound up with about 1,400 that met our inclusion criteria and we wanted to look at a couple of different things. One is to look at practice patterns and the other is to look out at outcomes.

One of the nice things about this database is its very well characterized within a single payer system. The other nice thing about this particular patient population is it does mirror the overall patient population in the United States. The general, there are some differences, one of the significant differences is the lack of out-of-pocket costs, so some drugs that are administered orally will have a significant co-pay in the real world, but our VA patients are able to get this for free.

So anyway, we looked at 1,400 patients. The timeline was from 2014 through 2018. So, that was essentially at the start of the CHAARTED era. So CHAARTED was, had a press release in December 2013 and then the data were officially released in May or June of 2014. Abiraterone data came out in 2017. So, this was in the docetaxel era in the beginning of the abiraterone era for those with metastatic castration-sensitive prostate cancer. And what we found was that overall, throughout the timeline of the study, 87% approximately received either ADT alone or ADT plus a traditional anti-androgen such as bicalutamide.

So the flip side is that only 13% received either docetaxel or abiraterone and that’s despite the, what I would consider, amazing data in terms of the effect on overall survival when either of those drugs plus nowadays, enzalutamide or apalutamide, are added early at the start of ADT. That number did get a little bit better through the end of the study, so that dropped from 87% overall to 77% at the end of the study that were receiving ADT or ADT plus a drug like bicalutamide, and this is long-term, it was not just for a flare. So there was an improvement, but still, it’s still only a quarter of patients that received what we would consider the best standard of care for the state.

Because the subsets who would receive docetaxel or abiraterone were very small, we were not able to really do an analysis of those particular patients versus, let’s say ADT alone, but we were able to look at ADT alone versus ADT plus anti-androgen and found that actually the addition of any drug, we would look at baseline characteristics, whether it’s anti-androgen, abiraterone or docetaxel, those patients look to have a little bit worse prostate cancer, so higher volume disease, more likely to involve viscera. So, that is one thing that we had to control for, also a trend for younger patients for the combined therapy, but analysis of ADT alone, or ADT plus an anti-androgen such as by bicalutamide, there was no difference in overall survival.

So, as I mentioned, those patients had slightly worse disease, but overall, unlike the meta-analysis from before that had a small survival benefit for what we used to call combined androgen blockade or some people call maximal androgen blockade, which is no longer the case, there was no difference in overall survival for that addition. It’s not what I would call level one data for that, but one might hypothesize because of the availability of more potent drugs following the initial hormone-sensitive treatment. So, and we did find that drugs like abiraterone, enzalutamide were the most common drugs for CRPC. So, upon progression after ADT with or without bicalutamide, that maybe that initial period of long-term treatment with an anti-androgen washes out because of that.

That’s the hypothesis, but we did not see a difference in overall survival. So, my bottom line would be that despite this patient population that gets more or less free drugs, docetaxel or abiraterone, it was only a very small proportion that even towards the end of the study period had received what I would consider standard of care. And, this comes on the heels of ASCO guidelines, about three weeks old coming out that really reinforce that in general, most patients should receive in addition to ADT, docetaxel, abiraterone, enzalutamide, or apalutamide.