ASCO GU 2023: Latest real world data in prostate cancer
Prof Phil Cornford – Royal Liverpool University Hospital, Liverpool, UK
Prof Laura-Maria Krabbe – University of Muenster Medical Center, Muenster, Germany
PC: Hello, and welcome to this ecancer presentation on castrate-resistant prostate cancer. We’re coming to you from San Francisco at the ASCO GU meeting and I’m Phil Cornford, a urologist from Liverpool.
LMK: Hi, my name is Laura Krabbe, I’m a urologist from the University of Muenster Medical Center in Germany.
PC: We’re going to start talking about non-metastatic castrate-resistant prostate cancer. We’ve seen the published data but there was some interesting data presented in Abstract 69 about real-world evidence for patients being treated with apalutamide. What did you think about it?
LMK: I always like to see real-world data a little bit after the trial data comes out because it gives us a little bit of an idea of how transferrable the study data is to the real-world population. In many instances, we actually see that the real-world population performs not as well as we see it in the trial population. That usually is not even a surprise because obviously trial populations are heavily selected to fit the patient profile that is ideally going to benefit from the tested medication. They also have to have quite a standard of physical performance, not too many
comorbidities in many cases, etc. So it’s a very selected population. In many real-world evidence datasets, we see that the real-world population performs less well. However, in the abstract that you mentioned we didn’t see such things and I thought that was really quite nice because we saw that the real-world population of about 400 patients receiving apalutamide for non-metastatic CRPC performed very, very close, and at some points even a couple of
percentage points better, than the trial population did. We saw that about 60% reached PSA drops of 90% or more and that was very consistent with the trial population that we saw in the SPARTAN trial. Also, we saw that after 24 months about 70% were still metastasis-free and that also fared very nicely with the trial population. So that was really encouraging to see how well the trial data are, in this real-world evidence study, transferrable to the real-world setting where we see our patients. So I thought this was quite nice, actually.
PC: I think everyone was really encouraged by it but it wasn’t the only data, there was other data presented, again looking at the other things that are possible, enzalutamide and darolutamide, that are also available for patients in this setting.
LMK: Yes, correct. There was another description where we had real world evidence from urology practices prescribing apalutamide, enzalutamide or darolutamide for M0 CRPC which is obviously consistent with the approvals and the trial spectrum that we saw. Again there we saw that all these three drugs are fairly similar in terms of applicability and also within the percentage points of patients having to discontinue the medication due to adverse events, due to the development of metastases or death. If you look at each of these separately the percentage points were very similar and that was also something that we saw within the trials that were designed very similarly and also then rendered very similar results. When you pulled it together so the percentage of patients having to discontinue due to adverse events, death or the development of metastases, it seemed that the patients on darolutamide had a little bit less frequently the need to discontinue the medication and it took them longer to get there. But that was only seen when you pooled all this together; when looked at separately it was very similar, I found. What was your take on it?
PC: I think you need to be just a bit careful about making those comparisons because these patients weren’t randomised like this. So there was a slight difference. I was really reassured that the data looked very similar to what we’d seen in the studies but drawing comparisons to say this drug is safer than that drug, this was not randomised, these were just people who happened to be allocated. I think on that basis those sorts of decisions are probably over-
interpreting what we saw in the data.
LMK: Yes, that’s why I thought it was really good that they didn’t just present the accumulative endpoints, presenting us with the total number of patients discontinuing for various reasons but also brought to us the breakdown of how many discontinued due to adverse events. I thought it was really reassuring to see how close these numbers were together within all three drugs and I think that supports what we’ve probably all put out and told our colleagues whenever asked about is there a one best option? We always said, no, we have three trials showing us exactly the same things and if there was a problem with tolerability whatsoever then probably the efficacy wouldn’t have been there because the people wouldn’t have gotten the drug long enough. So I think it was very consistent with what we saw and I loved the breakdown of the different reasons for discontinuation because that obviously is more granular
than just saying, ‘Well all of these people discontinued and there was a difference.’ So I thought
that was good that they reported this.
PC: Yes. There was some data on patients being managed for metastatic castrate-resistant prostate cancer, a slightly more advanced group, but again the data looked very similar to what we’ve seen in the studies. How did you view that?
LMK: Yes, so we had real-world evidence, especially also regarding how did people choose to treat in first line mCRPC which was, in this case, a novel hormonal agent. Then, interestingly, and that feeds to one of the questions, or maybe multiple questions, that we have – how do we sequence now that we have many drugs available? What’s the ideal sequence? Obviously, this real-world evidence will not give us the one holy grail answer to this but it can inform us somewhat. What I think the data showed was that, for one, it is very common practice to give one new hormonal agent after the other. That was a little bit surprising to me because we have known for quite some time that one NHT after the other doesn’t render really great effects and that’s what we saw in this study as well. So the first NHT rendered around eight months of progression-free survival and then the second drug down to four and then it went down further.
So no surprises here. What I felt a little bit concerned about was to see that 25% of patients in the second line received another new hormonal agent, only 14% received docetaxel chemotherapy, and over a third of patients received no further therapy. That, from a clinician standpoint who obviously is very trial avid and tries to expose patients to as many life-prolonging therapies as possible and wanted, I thought, hmm, already no further therapy after
the first mCRPC line – couldn’t we do better there?
PC: I think this really reflects what’s happening in the community, isn’t it? In studies when you look at patients involved in studies, because we’ve already said that they are a selected group,vthose people are fitter and they often go on to have other treatments. But in the real world if you don’t get a good first treatment then your chance of getting a second or third line becomes increasingly less likely. People are not getting the treatments that we need and we need to think, therefore, very carefully about what we give them as their first treatment. The idea that you would go on and give someone a second novel anti-androgen, knowing that the outcome is poor, is difficult to defend. I think in Europe we have said in the guidelines that we wouldn’t recommend doing second novel anti-androgens and in the UK it’s not actually allowed. NICE said there’s no benefit for doing that and I think that increasingly looks to be a good decision.
LMK: Yes.
PC: There was just a little bit of evidence from the TALAPRO and enzalutamide study. When we looked at their control arms and we showed that if you’d already had a novel anti-androgen and you then had enzalutamide as your control you got less than four months’ worth of improvement whereas if you had docetaxel as your control arm you got eight and a bit months until you had progression. I think that just emphasises the point that what you really need to think about is a new treatment in the different mechanisms of action for patients who are progressing on novel anti-androgens.
LMK: Yes, and I think it’s also a little bit about expectation management, to be honest, Because I feel that when I see that only 14% of people in this real-world evidence study that we saw received docetaxel chemotherapy, and I have to suggest that probably only a few of them received docetaxel in an mHSPC setting, then the physicians suggesting chemotherapy might be one issue, the patients being fit enough to receive chemotherapy may be another. But also patients really being afraid or against chemotherapy is a third. We as physicians have the role, also, to manage expectations. I’ve found that when you introduce the thought of at one point in your treatment course chemotherapy will be an important and valuable treatment choice for you early on, then the barriers of being afraid of receiving chemotherapy get broken down and people are more likely to be okay with accepting this as part of their treatment at some point in time. And for some, this might now be already in the mHSPC setting and for some, this might be later. But managing expectations and also the thought horizons of our patients is an important part of how we can expose more patients to as many potentially life-prolonging therapies as we can.
PC: I think that’s really important because we need to think about giving the best treatment up front when patients are fittest for it. We know that when treatments move from the castrate-resistant setting into the hormone-sensitive setting that you get a much bigger response. There will be a lot of discussion going forward about the use of intensified treatment for people with metastatic hormone-sensitive prostate cancer and clearly that will make a difference to what options they have when they develop castrate resistant. But we also know that lots of those patients will live a long time before they develop castrate resistant metastatic disease. Increasingly we need to talk to our patients about the benefits of early treatment and then getting the maximum out of the treatment. Because if you give docetaxel as a third or fourth-line treatment your chance of getting a prolonged response is much less than if you move it forward and give it for hormone sensitive prostate cancer.
LMK: Yes.
PC: Thank you very much for joining us, I hope that information was useful.
