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Hormone-Sensitive PC: What is the Standard of Care?

Panelists: Joe OSullivan, MD, FRCPI, FFRRCSI, FRCR, The Northern Ireland Cancer Centre, Belfast City Hospital; Johann de Bono, PhD, MB, ChB, Institute of Cancer Research, Royal Marsden Hospital; Chris Parker, MD, FRCR, MRCP, Institute of Cancer Research, Royal Marsden Hospital; Bertrand Tombal, MD, PhD, Cliniques Universitaires Saint-Luc
Published: Thursday, Oct 26, 2017



Transcript:

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: Moving on to a slightly different area, but an area where there have been an incredible amount of data in the last few years, what’s the best approach in metastatic hormone-sensitive prostate cancer? There is a lot of therapy in castration-resistant disease. But, Chris, what do you think the best approach to treating metastatic hormone-sensitive prostate cancer is? What are your thoughts?

Chris Parker, MD, FRCR, MRCP: That’s a hot topic right now. Of course, it was very easy until 2 years ago: ADT alone was the standard of care. For the last 2 years, since CHAARTED and STAMPEDE reported on docetaxel, ADT plus docetaxel was the new standard of care. And then the situation got more complicated this summer at ASCO with LATITUDE and STAMPEDE. So now we’ve got an advantage for ADT plus abiraterone compared to ADT alone. The obvious question to ask is, how does ADT plus docetaxel compare to ADT plus abiraterone? We did have some new data presented yesterday from STAMPEDE at this meeting, and these are patients who were randomized in STAMPEDE at a time when both the abiraterone comparison and the docetaxel comparison were open.

They happened to be randomized between abiraterone and docetaxel. Now, it’s only 560 patients. It’s not a fully powered study, but it’s the best we’ve got. The bottom line was that there was no significant difference in overall survival between the 2. So, right now, we’ve got 2 options. We’ve got abiraterone and docetaxel: We’ve got ADT plus docetaxel or ADT plus abiraterone, and they’re both acceptable options. From a clinical point of view, I’m happy to give either. If I was the patient, I would prefer abiraterone. I would regard it as more friendly, less toxic, and less getting in the way of my life.

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: It’s potentially treat until progression, which could be a few years.

Chris Parker, MD, FRCR, MRCP: Yes. We saw data from LATITUDE yesterday looking at quality of life, showing a clear advantage for ADT plus abiraterone versus ADT alone. Having said all that, the decision is going to be made for us by the payers, because if I was the payer, it’s absolutely obvious that ADT plus docetaxel is the standard of care.

Johann de Bono, PhD, MB, ChB: Can I challenge you on that, Chris? Because actually, it’s not A or B, it’s B then A or A then B. Indeed, the toxicity that we’re concerned about, both of us are concerned about, has to be managed at some point in the patient’s life. Actually, it may be more manageable for the patient to get docetaxel earlier, particularly if they’re a man who has to pay for their treatment, which is not uncommon—particularly in North America, but maybe not in the UK. Docetaxel is 18 weeks of an inexpensive generic drug, and abiraterone is probably $20,000 or $30,000, or more. In fact, probably a lot more over 2 years.

My biggest concern is that it’s not whether you get one versus the other, A or B. You’re going to get both at some point. And I would argue that, actually, we don’t know yet if early abiraterone is better than late abiraterone, because STAMPEDE and LATITUDE never asked that question. Therefore, that’s a question that has not been answered at all. In fact, we really haven’t yet properly compared docetaxel and abiraterone, because, as you said, the trial wasn’t powered to ask this question anyway. I do think that we’ve ended up with 2 standards of care, as you’ve rightly said, and we still haven’t moved the sphere forward very much through these trials, in my mind. Bertrand, do you want to comment?

Bertrand Tombal, MD, PhD: Something I’m very surprised about since STAMPEDE and CHAARTED is the reaction of patients with newly diagnosed metastatic prostate cancer when you say the reference treatment is ADT plus docetaxel. Very, very, very few patients refuse. One of the big advantages is that you know when you start, you know when you don’t, and then you can go on vacation. When you’re started on abiraterone, you’re going to come in, almost monthly, for 6-weekly visits to check your potassium. And there are also a lot of resources to be used, meaning that like many of people in the United Kingdom, you’ve got a beautiful residence in the South of France and are going to live 6 months there. You’re going to have to be organized.

This morning I was in the nonprostate GU session, and what we need now is that kind of pazopanib/sorafenib trial where we don’t look at FFS but we look at OS, where one group starts docetaxel and then gets abiraterone but in the APCCC consensus, meaning we all agree that you should give abiraterone very early when they’re becoming hormone resistant. We must do so and compare both sequences, because otherwise, there are pros and cons to the other. My anticipation is based on what the patient expects in life. If we are honest enough—and like Johann said, we say, “You’re going to get both. It’s up to you to decide whether you start with your chemotherapy and then abiraterone or you get abiraterone and then get chemotherapy.” I’m not so sure 100% of the patients will go to abiraterone.

Chris Parker, MD, FRCR, MRCP: I’m not sure that’s a question that’s worth asking in a big trial. I’d be very surprised if there’s going to be a meaningful benefit.

Bertrand Tombal, MD, PhD: No, there was no difference. There would be no difference.

Chris Parker, MD, FRCR, MRCP: The more interesting question, to be honest, would be looking at the combination. If you’re getting ADT plus docetaxel, is there a benefit from additional abiraterone?

Johann de Bono, PhD, MB, ChB: That trial will hopefully read out in the next 2 years, PEACE1. I agree, that’s a very important question, although I do worry there’s a very good reason why giving those 2 drugs together could be deleterious. I’m hoping that’s a positive trial. I think it could be a positive trial, but we’ve learned from other diseases, including breast cancer, that combinations are not necessarily better than serial therapy, one after the other. It does really worry me that we’re giving a lot of our best drugs very early to these patients, very early in their disease, and they’re ending up with no therapy options left. I do think we have to be quite careful about that.

Transcript Edited for Clarity 

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Transcript:

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: Moving on to a slightly different area, but an area where there have been an incredible amount of data in the last few years, what’s the best approach in metastatic hormone-sensitive prostate cancer? There is a lot of therapy in castration-resistant disease. But, Chris, what do you think the best approach to treating metastatic hormone-sensitive prostate cancer is? What are your thoughts?

Chris Parker, MD, FRCR, MRCP: That’s a hot topic right now. Of course, it was very easy until 2 years ago: ADT alone was the standard of care. For the last 2 years, since CHAARTED and STAMPEDE reported on docetaxel, ADT plus docetaxel was the new standard of care. And then the situation got more complicated this summer at ASCO with LATITUDE and STAMPEDE. So now we’ve got an advantage for ADT plus abiraterone compared to ADT alone. The obvious question to ask is, how does ADT plus docetaxel compare to ADT plus abiraterone? We did have some new data presented yesterday from STAMPEDE at this meeting, and these are patients who were randomized in STAMPEDE at a time when both the abiraterone comparison and the docetaxel comparison were open.

They happened to be randomized between abiraterone and docetaxel. Now, it’s only 560 patients. It’s not a fully powered study, but it’s the best we’ve got. The bottom line was that there was no significant difference in overall survival between the 2. So, right now, we’ve got 2 options. We’ve got abiraterone and docetaxel: We’ve got ADT plus docetaxel or ADT plus abiraterone, and they’re both acceptable options. From a clinical point of view, I’m happy to give either. If I was the patient, I would prefer abiraterone. I would regard it as more friendly, less toxic, and less getting in the way of my life.

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: It’s potentially treat until progression, which could be a few years.

Chris Parker, MD, FRCR, MRCP: Yes. We saw data from LATITUDE yesterday looking at quality of life, showing a clear advantage for ADT plus abiraterone versus ADT alone. Having said all that, the decision is going to be made for us by the payers, because if I was the payer, it’s absolutely obvious that ADT plus docetaxel is the standard of care.

Johann de Bono, PhD, MB, ChB: Can I challenge you on that, Chris? Because actually, it’s not A or B, it’s B then A or A then B. Indeed, the toxicity that we’re concerned about, both of us are concerned about, has to be managed at some point in the patient’s life. Actually, it may be more manageable for the patient to get docetaxel earlier, particularly if they’re a man who has to pay for their treatment, which is not uncommon—particularly in North America, but maybe not in the UK. Docetaxel is 18 weeks of an inexpensive generic drug, and abiraterone is probably $20,000 or $30,000, or more. In fact, probably a lot more over 2 years.

My biggest concern is that it’s not whether you get one versus the other, A or B. You’re going to get both at some point. And I would argue that, actually, we don’t know yet if early abiraterone is better than late abiraterone, because STAMPEDE and LATITUDE never asked that question. Therefore, that’s a question that has not been answered at all. In fact, we really haven’t yet properly compared docetaxel and abiraterone, because, as you said, the trial wasn’t powered to ask this question anyway. I do think that we’ve ended up with 2 standards of care, as you’ve rightly said, and we still haven’t moved the sphere forward very much through these trials, in my mind. Bertrand, do you want to comment?

Bertrand Tombal, MD, PhD: Something I’m very surprised about since STAMPEDE and CHAARTED is the reaction of patients with newly diagnosed metastatic prostate cancer when you say the reference treatment is ADT plus docetaxel. Very, very, very few patients refuse. One of the big advantages is that you know when you start, you know when you don’t, and then you can go on vacation. When you’re started on abiraterone, you’re going to come in, almost monthly, for 6-weekly visits to check your potassium. And there are also a lot of resources to be used, meaning that like many of people in the United Kingdom, you’ve got a beautiful residence in the South of France and are going to live 6 months there. You’re going to have to be organized.

This morning I was in the nonprostate GU session, and what we need now is that kind of pazopanib/sorafenib trial where we don’t look at FFS but we look at OS, where one group starts docetaxel and then gets abiraterone but in the APCCC consensus, meaning we all agree that you should give abiraterone very early when they’re becoming hormone resistant. We must do so and compare both sequences, because otherwise, there are pros and cons to the other. My anticipation is based on what the patient expects in life. If we are honest enough—and like Johann said, we say, “You’re going to get both. It’s up to you to decide whether you start with your chemotherapy and then abiraterone or you get abiraterone and then get chemotherapy.” I’m not so sure 100% of the patients will go to abiraterone.

Chris Parker, MD, FRCR, MRCP: I’m not sure that’s a question that’s worth asking in a big trial. I’d be very surprised if there’s going to be a meaningful benefit.

Bertrand Tombal, MD, PhD: No, there was no difference. There would be no difference.

Chris Parker, MD, FRCR, MRCP: The more interesting question, to be honest, would be looking at the combination. If you’re getting ADT plus docetaxel, is there a benefit from additional abiraterone?

Johann de Bono, PhD, MB, ChB: That trial will hopefully read out in the next 2 years, PEACE1. I agree, that’s a very important question, although I do worry there’s a very good reason why giving those 2 drugs together could be deleterious. I’m hoping that’s a positive trial. I think it could be a positive trial, but we’ve learned from other diseases, including breast cancer, that combinations are not necessarily better than serial therapy, one after the other. It does really worry me that we’re giving a lot of our best drugs very early to these patients, very early in their disease, and they’re ending up with no therapy options left. I do think we have to be quite careful about that.

Transcript Edited for Clarity 
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