Analyzing Quality of Life and Survival from CHAARTED Prostate Cancer Trial - Daniel Sentana Lledo
July 3, 2023
Alicia Morgans and Daniel Sentana Lledo discuss a groundbreaking analysis on data from the CHAARTED study that examined how quality of life impacts survival in metastatic hormone-sensitive prostate cancer patients. Interestingly, patients with better quality of life scores at three months exhibited longer survival times. However, the role of docetaxel (a chemotherapeutic) treatment in this finding is nuanced. For patients with low quality of life scores, docetaxel appears to significantly improve survival, irrespective of their baseline quality of life. In contrast, for those with good quality of life, the survival benefits of docetaxel are less clear. While these findings are still hypothesis-generating and require prospective validation, they can potentially influence frontline treatment decisions, especially in light of newer treatment options like anti-androgens. Dr. Sentana Lledo emphasizes the critical importance of maintaining and improving patients' quality of life while extending survival.
Biographies:
Daniel Sentana Lledo, MD, Clinical Fellow in Medicine, Beth Israel Deaconess Medical Center, Boston, MA
Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts
Biographies:
Daniel Sentana Lledo, MD, Clinical Fellow in Medicine, Beth Israel Deaconess Medical Center, Boston, MA
Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts
Read the Full Video Transcript
Alicia Morgans: Hi, I'm so excited to be here with Dr. Daniel Sentana, who's joining me from Beth Israel Deaconess Medical Center in Boston. Thank you so much for talking with me today.
Daniel Sentana Lledo: Absolutely, Dr. Morgans, thank you for having me.
Alicia Morgans: Well, wonderful. So Daniel, you did a really fantastic analysis that was presented as a poster discussion at ASCO 2023. It was an analysis of CHAARTED data, and trying to really dig into some of the rich quality of life analyses that were embedded within that trial. Can you tell me a little bit about, what was CHAARTED, just to remind everyone?
Daniel Sentana Lledo: Oh, sure.
Alicia Morgans: Very, very briefly. And then, what were you looking into in quality of life data?
Daniel Sentana Lledo: Absolutely. So CHAARTED is a study that came out about nine years ago or so, that was looking at chemo hormonal therapy, which that was androgen deprivation therapy with docetaxel in the metastatic hormone-sensitive prostate cancer patients. And really, after that study showed a tremendous overall survival advantage with chemo hormonal versus ADT, it was accepted as standard of care, knowing that further studies sort of just reduced that to the high volume population of disease.
And as part of the trial, there was patient report outcomes that were collected every three months in the first year, which had been analyzed before. But what we did in this abstract was, sort of join both things. So we wanted to see if the patient reported outcomes had any prognostic implications? Meaning, did the patients with different quality of life lead to different survivals? And we specifically focused on how the chemotherapy impacted this. And so, what we did was, focus on the baseline on the three-month time period, so baseline, because we expected that would be the time where patients would have the most symptoms from their disease, and at three months, where it was the peak toxicity from docetaxel.
Alicia Morgans: Great. So what did you find? Did the quality of life have any prognostic implication? Were there any changes in quality of life that might have also made a difference, in terms of their overall prognosis? And how did chemo come into play?
Daniel Sentana Lledo: Sure. So what we saw was interestingly, not exactly at baseline, but at three months, there was an association between having better quality of life scores and having longer survival. And interestingly, when we sort of pieced it out a little bit, as you said, by treatment, well first, to say that was this association was independent of treatment and a couple other clinical variables that have prognostic implications. But when we pieced it out by how does treatment affect this? So patients with the best quality of life that had received docetaxel had comparable survival, that those had had low quality of life and also got docetaxel. So I think my message from that is, even people with low quality of life, they should get docetaxel, because you will get them through it and they have improved survival.
On the other hand, the patients that just got ADT by itself, there was drastically different survival probably. So people that had very good quality of life, they had decent survival, but those that had poor quality of life had, their survival was very different. And an interesting corollary from all of this is that, when we look at just best quality of life patients, you can even argue from our data, that maybe docetaxel is not necessary in this subgroup, just because of how well they did, just by being a prognostic quality on itself. And as I said, on the other hand, patients with poor quality of life, they do, they should absolutely get docetaxel.
Alicia Morgans: I think that's so important. And just to sort of restate that, our sickest patients that come in with the most pain, with the poorest overall quality of life, which was one of the things that were measured within CHAARTED, that fact P overall quality of life, those patients treated with ADT and docetaxel had a substantial benefit from that docetaxel addition. So sometimes I think we think, oh, those patients who are super sick, maybe they can't tolerate it. And if they're on the border, maybe we should push to give them some of that intensive therapy, because a lot of that quality of life may be driven by the symptoms of their cancer in some cases.
Daniel Sentana Lledo: Yeah, totally. I think overall, I think some of the things to think about is, that there's a retrospective analysis, so this should be validated prospectively, and we cannot make blanket statements for everyone. But I think, to your point, this hopefully will influence a little bit how we think about the type of treatment we should give front-line to metastatic hormone-sensitive patients.
And I think, this is particularly relevant nowadays, where we're in this phase of adding additional anti-androgens with what is called a triplet therapy options. So it would be very interesting to see if the same holds true prospectively looking at this subgroup. Meaning, patients that got both docetaxel and antiandrogen, whether it's darolutamide or abiraterone, do you really need to give them the chemo? It's going to be hard to go against what is currently a standard. But I think if you can longitudinally track patient reported outcomes and say that those patients with the best quality of life, why do we do all of this that we do is to, when someone has metastatic disease, is essentially, to keep their best quality of life, and extend their life as long as possible. So perhaps the detriments of giving them chemotherapy are not warranted at that time point.
Alicia Morgans: It is very much hypothesis generated.
Daniel Sentana Lledo: Totally.
Alicia Morgans: And you have my mind spinning on some trials that we could apply these analyses to. I wonder if the same would hold true for those AR receptor and signaling inhibitors? Because these are different toxicity profile.
Daniel Sentana Lledo: Totally.
Alicia Morgans: And may have really significant benefits, in terms of disease control, obviously, distinct from chemotherapy. So definitely, questions that we can ask, perhaps in different data sets, to see if we can understand whether the same is true in that good prognosis, good quality of life population. How much do we need to intensify? And that good quality of life patient population has already been demonstrated in multiple settings to have a good prognosis overall. So really interesting.
Now, I wonder, do you have comments on how this had any interplay, or did not have an interplay, with high and low volume disease? Which, of course, was a centerpiece of the CHAARTED analysis, raised a lot of controversy for many years.
Daniel Sentana Lledo: Yes. So actually, that's a great question, because obviously, wanted our absolute results to be the most applicable to how this therapy is used nowadays. And to your point, it's probably just reserved to high volume patients by national guidelines. And in fact, most of the patients we analyze, whether they had the best quality of life or the lowest quality of life, up to two thirds to three quarters of patients were high volume. So I think we can comfortably say that this is applicable to those patients' population. And the results from our abstract would apply to the population that would get this type of treatment nowadays.
Alicia Morgans: Wonderful. So as you're thinking through what you found in this abstract, in this presentation, and, of course, as you're preparing the manuscript, what would your clinical implications and take home messages be? How do you use this information in the clinic?
Daniel Sentana Lledo: Well, as I said, I think this is an hypothesis generating interesting finding, but I think it could have implications to how we practice nowadays. I think if a patient comes to your clinic, they have newly de novo metastatic disease, so newly diagnosed, but they feel completely fine, it is just scans that found it, perhaps you can talk through them and say, this is what we normally do, but we have some early evidence that perhaps this treatment intensification would be too toxic, sick, and not necessarily lead to significant survival benefits.
On the contrary, I would say, if I have a patient who is very sick from their newly diagnosed cancer, then I would say, "No one likes to get this type of treatment. But at the same time, I know that if we get you through it, and we are on top of your symptoms that you get from the treatment, then we will get you through it. And it has tremendous implications to how long you will survive with this."
Alicia Morgans: Wow, wonderful. Well, thank you so much for sharing your expertise, for doing this work. It is very, very interesting. I sincerely appreciate your time and your expertise.
Daniel Sentana Lledo: Thank you so much.
Alicia Morgans: Hi, I'm so excited to be here with Dr. Daniel Sentana, who's joining me from Beth Israel Deaconess Medical Center in Boston. Thank you so much for talking with me today.
Daniel Sentana Lledo: Absolutely, Dr. Morgans, thank you for having me.
Alicia Morgans: Well, wonderful. So Daniel, you did a really fantastic analysis that was presented as a poster discussion at ASCO 2023. It was an analysis of CHAARTED data, and trying to really dig into some of the rich quality of life analyses that were embedded within that trial. Can you tell me a little bit about, what was CHAARTED, just to remind everyone?
Daniel Sentana Lledo: Oh, sure.
Alicia Morgans: Very, very briefly. And then, what were you looking into in quality of life data?
Daniel Sentana Lledo: Absolutely. So CHAARTED is a study that came out about nine years ago or so, that was looking at chemo hormonal therapy, which that was androgen deprivation therapy with docetaxel in the metastatic hormone-sensitive prostate cancer patients. And really, after that study showed a tremendous overall survival advantage with chemo hormonal versus ADT, it was accepted as standard of care, knowing that further studies sort of just reduced that to the high volume population of disease.
And as part of the trial, there was patient report outcomes that were collected every three months in the first year, which had been analyzed before. But what we did in this abstract was, sort of join both things. So we wanted to see if the patient reported outcomes had any prognostic implications? Meaning, did the patients with different quality of life lead to different survivals? And we specifically focused on how the chemotherapy impacted this. And so, what we did was, focus on the baseline on the three-month time period, so baseline, because we expected that would be the time where patients would have the most symptoms from their disease, and at three months, where it was the peak toxicity from docetaxel.
Alicia Morgans: Great. So what did you find? Did the quality of life have any prognostic implication? Were there any changes in quality of life that might have also made a difference, in terms of their overall prognosis? And how did chemo come into play?
Daniel Sentana Lledo: Sure. So what we saw was interestingly, not exactly at baseline, but at three months, there was an association between having better quality of life scores and having longer survival. And interestingly, when we sort of pieced it out a little bit, as you said, by treatment, well first, to say that was this association was independent of treatment and a couple other clinical variables that have prognostic implications. But when we pieced it out by how does treatment affect this? So patients with the best quality of life that had received docetaxel had comparable survival, that those had had low quality of life and also got docetaxel. So I think my message from that is, even people with low quality of life, they should get docetaxel, because you will get them through it and they have improved survival.
On the other hand, the patients that just got ADT by itself, there was drastically different survival probably. So people that had very good quality of life, they had decent survival, but those that had poor quality of life had, their survival was very different. And an interesting corollary from all of this is that, when we look at just best quality of life patients, you can even argue from our data, that maybe docetaxel is not necessary in this subgroup, just because of how well they did, just by being a prognostic quality on itself. And as I said, on the other hand, patients with poor quality of life, they do, they should absolutely get docetaxel.
Alicia Morgans: I think that's so important. And just to sort of restate that, our sickest patients that come in with the most pain, with the poorest overall quality of life, which was one of the things that were measured within CHAARTED, that fact P overall quality of life, those patients treated with ADT and docetaxel had a substantial benefit from that docetaxel addition. So sometimes I think we think, oh, those patients who are super sick, maybe they can't tolerate it. And if they're on the border, maybe we should push to give them some of that intensive therapy, because a lot of that quality of life may be driven by the symptoms of their cancer in some cases.
Daniel Sentana Lledo: Yeah, totally. I think overall, I think some of the things to think about is, that there's a retrospective analysis, so this should be validated prospectively, and we cannot make blanket statements for everyone. But I think, to your point, this hopefully will influence a little bit how we think about the type of treatment we should give front-line to metastatic hormone-sensitive patients.
And I think, this is particularly relevant nowadays, where we're in this phase of adding additional anti-androgens with what is called a triplet therapy options. So it would be very interesting to see if the same holds true prospectively looking at this subgroup. Meaning, patients that got both docetaxel and antiandrogen, whether it's darolutamide or abiraterone, do you really need to give them the chemo? It's going to be hard to go against what is currently a standard. But I think if you can longitudinally track patient reported outcomes and say that those patients with the best quality of life, why do we do all of this that we do is to, when someone has metastatic disease, is essentially, to keep their best quality of life, and extend their life as long as possible. So perhaps the detriments of giving them chemotherapy are not warranted at that time point.
Alicia Morgans: It is very much hypothesis generated.
Daniel Sentana Lledo: Totally.
Alicia Morgans: And you have my mind spinning on some trials that we could apply these analyses to. I wonder if the same would hold true for those AR receptor and signaling inhibitors? Because these are different toxicity profile.
Daniel Sentana Lledo: Totally.
Alicia Morgans: And may have really significant benefits, in terms of disease control, obviously, distinct from chemotherapy. So definitely, questions that we can ask, perhaps in different data sets, to see if we can understand whether the same is true in that good prognosis, good quality of life population. How much do we need to intensify? And that good quality of life patient population has already been demonstrated in multiple settings to have a good prognosis overall. So really interesting.
Now, I wonder, do you have comments on how this had any interplay, or did not have an interplay, with high and low volume disease? Which, of course, was a centerpiece of the CHAARTED analysis, raised a lot of controversy for many years.
Daniel Sentana Lledo: Yes. So actually, that's a great question, because obviously, wanted our absolute results to be the most applicable to how this therapy is used nowadays. And to your point, it's probably just reserved to high volume patients by national guidelines. And in fact, most of the patients we analyze, whether they had the best quality of life or the lowest quality of life, up to two thirds to three quarters of patients were high volume. So I think we can comfortably say that this is applicable to those patients' population. And the results from our abstract would apply to the population that would get this type of treatment nowadays.
Alicia Morgans: Wonderful. So as you're thinking through what you found in this abstract, in this presentation, and, of course, as you're preparing the manuscript, what would your clinical implications and take home messages be? How do you use this information in the clinic?
Daniel Sentana Lledo: Well, as I said, I think this is an hypothesis generating interesting finding, but I think it could have implications to how we practice nowadays. I think if a patient comes to your clinic, they have newly de novo metastatic disease, so newly diagnosed, but they feel completely fine, it is just scans that found it, perhaps you can talk through them and say, this is what we normally do, but we have some early evidence that perhaps this treatment intensification would be too toxic, sick, and not necessarily lead to significant survival benefits.
On the contrary, I would say, if I have a patient who is very sick from their newly diagnosed cancer, then I would say, "No one likes to get this type of treatment. But at the same time, I know that if we get you through it, and we are on top of your symptoms that you get from the treatment, then we will get you through it. And it has tremendous implications to how long you will survive with this."
Alicia Morgans: Wow, wonderful. Well, thank you so much for sharing your expertise, for doing this work. It is very, very interesting. I sincerely appreciate your time and your expertise.
Daniel Sentana Lledo: Thank you so much.