Latest advances in mHSPC from ASCO GU 2020
Dr Eleni Efstathiou – MD Anderson Cancer Center, Houston, USA
Prof Axel Merseburger – University Hospital Schleswig-Holstein, Lübeck, Germany
EE: Hello and happy Valentine’s Day and for the coming weekend, of course, from San Francisco. I’m also joined by one of my esteemed colleagues, Dr Axel Merseburger who is a surgical oncologist, a urologic oncologist, as you know very well an expert in our field. We have been through the first days of GU ASCO, it’s still ongoing. It is, as always, a very interesting meeting to interact, to produce not only new data but also plan new studies. So, Axel, as a professor and an expert in the field, you come from the scholarly side of things. We just heard last week that apalutamide got the approval in the indication for use, not just now in the non-metastatic CRPC but also in the very important metastatic hormone naïve prostate cancer space. What are your thoughts and what are the implications for our patients and our providers, our practitioners, of course?
AM: So, Eleni, thanks for having me here; quite a pleasure to exchange news with you, as always. So we have had, I would say, a year of mHSPC in 2019 with the ARCHES trial being presented a year ago in the same city we are sitting right now. We had ENZAMET at ASCO presented by Chris Sweeney which changed a lot and also the New England publication and presentation by Kim Chi on TITAN. As we recall, TITAN included more than 1,000 men with metastatic prostate cancer. They could have been treated at the primary, they could have had radiation, prior docetaxel, and they were randomised in a one-to-one fashion towards apalutamide and ADT or, at that time, standard – just ADT. This resulted in really a remarkable radiographic progression free survival benefit for the arm that received the combination of apalutamide and ADT; very highly statistically significant overall survival as well for the combination. So we have a new situation in mHSPC in 2020 where we are fortunate to just have this approval a couple of weeks ago in Europe to use apalutamide in those patients with metastatic hormone sensitive prostate cancer.
EE: So, of course, you were just discussing before we walked in this interview how you are able to now prescribe. But you are also very experienced because you’ve been part of all the trials, you’ve used it a lot in that setting and you keep also interrogating the disease with other such agents. But for those physicians who are going to be now using it for the first time, and it looks like the impact is really remarkable when it comes to overall survival. On top of that I think we all agree that now, in 2020, we’ve had eleven phase III trials with novel androgen signalling inhibitors, all positive, and the data is compelling that as you come earlier in the disease the impact is higher and stronger. So do you think there is still a place for a physician to tell a patient, ‘I’m only going to give you leuprolide’ or an LHRH agonist or antagonist, I’m going to say? As a scholar, what would your thoughts be?
AM: That’s a very important point you are tickling out there because we still should somehow look at the risk and the volume. We have the high risk situation and we have the low volume and high volume patients with a lot of metastasis or high PSA, visceral disease, high Gleason. Here I can only think of a situation where you have a low volume oligometastatic disease patient and low risk profile, which is very rare, where, up to TITAN, we would have no real indication for abiraterone or docetaxel in this setting.
EE: [?? 4:10]
AM: Correct, only this. It would probably work, we have those STAMPEDE data also showing that there is an effect of docetaxel. So I think definitely, being on your side, ADT is not enough for mHSPC patients. Now we have the TITAN data where we have an all-comer indication. So regardless of prior therapy, regardless of volume, you don’t really have to think anymore for speaking urologist or surgeon oncologist which is easy, you don’t have to really calculate a lot and count the bone mets. So you can use it in all patients with, let’s say, just an oligometastatic situation. So this is easy, this is good. Also what we’ve seen yesterday, the presentation from Dr Aggarwal on the PFS2 and I have found it to be very interesting looking at this PFS2. So not only the first progression but also the second progression where, regardless of the second treatment, whether it is chemotherapy or a second hormone therapy, the benefit for the combination with abiraterone was proven and just demonstrates this.
EE: Which speaks more to earlier is better. It is like we should not wait. You have been also in these meetings where we’re sitting together to figure out how we can promote education to our fellow colleagues who are out there in the community and don’t have the privileges that we entertain in our institutions and need to know how to act. So we’re seeing that in the United States where we have had access to the novel androgen signalling inhibitors for now almost… we’re getting into the third year, the uptake is not what it should be. We only see 10-20% of prescription and no use of chemotherapy, by the way, which there may be a place. You bring it all together because in Germany the urologists also treat with cytotoxics so you have the choice. It’s not like you’re limited like others. So I think you’re in the perfect position to comment on how we can go about getting better.
AM: You mentioned this evidence and it’s somehow scary or surprising that after five years post-CHAARTED trial there is still a lot of hesitation to use those novel agents. So I think, especially within those hormonal treatment options we have now, we should be going along with the evidence, with educating the doctors and speaking to the patient that we really have an overall survival benefit that we can slow progression of the disease. Here, and you mentioned M0 CRPC where we speak about MFS and those endpoints which are not a deadly disease, but in metastatic prostate cancer we really have a deadly disease with an overall survival median of about three years. So here it’s well invested to educate the colleagues to start early and that ADT is not enough and you should combine either with apalutamide, docetaxel or enzalutamide as some options.
EE: So to that point, because also you have the opportunity to experience both the cytotoxic and also all the novel androgen signalling inhibitors in your practice, do you have any concerns with the use of apalutamide? Because we’ve seen the numbers and just my humble opinion is when the patient just starts LHRH there is an impact on the patient regardless of the addition of apalutamide and any other inhibitor. The added toxicity is not that remarkable, it’s limited, but would you have any special considerations for subgroups of patients?
AM: I think a patient and also doctors should be aware of some different toxicities, for example the rash which is occurring in about 20% of the patients. It’s good to handle but you have to know when the patient develops a rash.
EE: And earlier is better there too, right?
AM: That’s true. And we’ve experienced once you stop and maybe use corticosteroids and you start again, in most cases the rash never appears again. It’s odd, I don’t know the mechanism of action behind that but it’s something that happens. So what you mentioned, I totally agree. The biggest impact for the man with metastatic prostate cancer is the ADT because it changes a lot – metabolically, libido wise, with regards to weight gain and everything which is associated to the ADT. When you add on another androgen targeting agent the difference, you have a good combination there, totally different than the side effects you have with docetaxel.
EE: So you’re very comfortable giving it, right?
EE: Who would you have follow? Is it you, is it your fellows, like in your practice, the toxicity monitoring? You have to see these patients, you have to prevent them from other things happening – how would you go about doing it?
AM: Initially I recommend to see the patients every couple of weeks to see how they feel and draw blood and discuss side effects and talk to them.
EE: Mainly because, I’m sorry to interrupt again, they’re starting something new, a new journey?
EE: It’s not because of the specific drugs, they need to get accustomed.
AM: True. Then you have every three months the ADT, maybe you have bisphosphonates, like some substances for bone protection where you need to see the patient every month. So you have a lot of intervals to have a chance to see the patient. Also every three months maybe an imaging, it’s good advice to see how the disease is behaving.
EE: I’ve always said that urologists know the disease better sometimes than oncologists but this is probably going to go public that I said it. So I would say that it has to do with the specific physicians, we should agree, the [?? 10:03] right? That’s the whole point.
AM: Yes, and with a multidisciplinary, working together as we have shown today, it’s important and that’s what we also use in the German setting – an MDT once a week.
EE: You’re right. Well I’m sure that Europe is going to exhibit very high standards and education; thanks to scholars like you we’ll have very high levels. Thank you so much for this discussion. Thank you all. Thank you.
AM: Thanks a lot, thanks Eleni.