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The Approval of Apalutamide for Metastatic CSPC

Insights From:Alicia Morgans, MD, MPH, Northwestern University Feinberg School of Medicine; Matthew R. Smith, MD, PhD, Massachusetts General Hospital Cancer Center
Published: Monday, Jan 13, 2020



Transcript:

Matthew R. Smith, MD, PhD:
TITAN is a global, randomized controlled trial that compared the addition of apalutamide versus placebo with androgen deprivation therapy [ADT] in men with metastatic castration-sensitive prostate cancer [mCSPC]. The real rationale here is to look at intensification of initial systemic treatment in men with metastatic prostate cancer at the time of initial diagnosis. The patients all received androgen deprivation therapy and then were randomized to apalutamide or placebo, with the primary outcomes of progression-free survival and overall survival.

The study showed significant improvement in overall survival and a safety profile with really no new signals compared with what was already known with apalutamide. On the basis of these compelling TITAN results, apalutamide has been approved by the FDA for the treatment of men with metastatic castration-sensitive prostate cancer. We can now add apalutamide, as a therapeutic option, to another drug that’s been approved in this setting: abiraterone acetate plus prednisone. And although not formally approved in this setting, docetaxel has also shown efficacy in the same setting.

Alicia Morgans, MD, MPH: We just heard at ESMO [the European Society for Medical Oncology Congress] this year that the patient-reported outcomes data are available now for the TITAN study. This is really important because apalutamide was just approved for metastatic castration-sensitive prostate cancer and is a new option for us to use in the treatment of this patient population. Patient-reported outcomes really reflect the patient’s day-to-day experience from their own perspective, not the assessment of the clinician. And it gives them an opportunity to say whether something is making them feel poorly even if we’re not detecting that in our adverse-event assessment in the clinical trials.

Importantly, in TITAN, these patient-reported outcomes suggested that patients felt similarly whether they were getting an additional drug or ADT alone. The reason this is so important is that when we treat patients and we prolong their survival, we want to make sure that, at a minimum, we’re not making them feel worse or making their lives worse. Sometimes it has to be worse in the short term to be better in the long term. But in this case, I think it’s really positive to think that they actually feel pretty well every day, or are generally asymptomatic, as we saw, and don’t feel worse than those patients who are getting ADT alone.

Additionally, they reported that the fatigue of treatment with apalutamide was not worse than for patients receiving ADT alone. This is important because, again, fatigue has been identified as a potential problem with some of the drugs that are targeting the androgen receptor [AR] in this population. Knowing that fatigue isn’t worse is just another way for us to know that this drug is highly effective in prolonging survival but also effective in maintaining quality of life for these patients.

Elizabeth Heath, MD: Now we’re in a different space. We’re now in the metastatic castration-sensitive space, for which prior to all the new emerging data, treatment really was docetaxel based or abiraterone. The important part of the TITAN study, especially as it relates to the PRO [patient-reported outcomes] data, is we are really concerned about patients in the long term. How do they feel? What adverse effects are going on?

It’s great to say, “Here’s your medication. I’ll see you later,” but patients have to live with the adverse effects. Having the quality-of-life parameters, other facts that are measured, is important for these patients because we don’t want to just prescribe medications. We want to make sure we’re prescribing them and that they’re tolerating therapy, and that their quality of life and their impact isn’t negative. And that’s really important because sometimes, fortunately, these men are on therapy for years, and that’s what we hope for. But it can’t be at any cost. So to show that there’s really no difference compared with placebo is really important.

I’m not sure the data change much. I think it’s supportive, again. When all the data points come in and you feel as though this is what you’ve been doing, it gives you a sense of comfort that you’re on the right track and that you’re not harming the patient. But you’re getting the utility of, “Oh, wow: the survival benefit, the PFS [progression-free survival], all the things that matter to us as oncologists are still there.” Sometimes you get that but at a big cost. There are other studies that show that other drugs don’t become as standard in mainstream. But in this case, I think it’s just supportive data that make us all feel confident that we’re on the right track.

Matthew R. Smith, MD, PhD: The patient-reported outcome data from TITAN showed that patients begin the study with a relatively high, global quality of life, and that their quality of life is maintained throughout the course of the study. There are really no meaningful differences between placebo and apalutamide, which is important, and meaningful information to help understand the impact of this treatment. It appears that these well-documented benefits of improved progression-free survival and overall survival come at relatively little cost in patient quality of life. Now, it is worth mentioning that some of these measures are relatively insensitive to show subtle changes in quality of life. To get a full sense of the tolerability of therapy, one should also look at the safety information for apalutamide and any other drug in this setting.

The approval of apalutamide in metastatic castration-sensitive prostate cancer based on the results of the pivotal TITAN trial provide an additional option for patients in this really important disease state. There are differences in tolerability between agents. There are some patients who, perhaps, are not good candidates for docetaxel or abiraterone acetate plus prednisone, based on their age and comorbidities. And so apalutamide’s efficacy and safety data provide a nice option for some patients who wouldn’t be good candidates for these other treatments and, arguably, would be a good option for patients who also might be a candidate for those other therapies. As a clinician, it’s always attractive to have good, effective, and safe options, so we can provide the most benefit to the largest group of patients in this setting.

Alicia Morgans, MD, MPH: When clinicians are choosing treatments for metastatic CSPC, I think it’s important for them to have the opportunity to review the efficacy data—how well the drug works in prolonging survival—but also the patient-reported outcome data that reflects how the patients feel and how their quality of life will be. This data are really critically important when physicians have those conversations with patients about what life will be like when they choose 1 drug for treatment of this disease versus another. The information we have from TITAN suggests that quality of life is maintained and that fatigue is not worse with the treatment of mCSPC with apalutamide. This gives patients and clinicians information that they need to potentially choose this treatment or another treatment. They have the details and data that they need to make that choice.

This is also important because the FDA has recently approved this drug. And for patients, it means more options, more things to consider, more ways to find the right drug for them. Without these kinds of approvals and without this progress, patients are left to have only the drug that we have available. In this case, we have multiple drugs available with more on the horizon, likely. I think it’s an exciting and wonderful time for patients to be able to choose, again, the right drug for him and for his life, knowing both the quality-of-life data and the efficacy data.


Transcript Edited for Clarity
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Transcript:

Matthew R. Smith, MD, PhD:
TITAN is a global, randomized controlled trial that compared the addition of apalutamide versus placebo with androgen deprivation therapy [ADT] in men with metastatic castration-sensitive prostate cancer [mCSPC]. The real rationale here is to look at intensification of initial systemic treatment in men with metastatic prostate cancer at the time of initial diagnosis. The patients all received androgen deprivation therapy and then were randomized to apalutamide or placebo, with the primary outcomes of progression-free survival and overall survival.

The study showed significant improvement in overall survival and a safety profile with really no new signals compared with what was already known with apalutamide. On the basis of these compelling TITAN results, apalutamide has been approved by the FDA for the treatment of men with metastatic castration-sensitive prostate cancer. We can now add apalutamide, as a therapeutic option, to another drug that’s been approved in this setting: abiraterone acetate plus prednisone. And although not formally approved in this setting, docetaxel has also shown efficacy in the same setting.

Alicia Morgans, MD, MPH: We just heard at ESMO [the European Society for Medical Oncology Congress] this year that the patient-reported outcomes data are available now for the TITAN study. This is really important because apalutamide was just approved for metastatic castration-sensitive prostate cancer and is a new option for us to use in the treatment of this patient population. Patient-reported outcomes really reflect the patient’s day-to-day experience from their own perspective, not the assessment of the clinician. And it gives them an opportunity to say whether something is making them feel poorly even if we’re not detecting that in our adverse-event assessment in the clinical trials.

Importantly, in TITAN, these patient-reported outcomes suggested that patients felt similarly whether they were getting an additional drug or ADT alone. The reason this is so important is that when we treat patients and we prolong their survival, we want to make sure that, at a minimum, we’re not making them feel worse or making their lives worse. Sometimes it has to be worse in the short term to be better in the long term. But in this case, I think it’s really positive to think that they actually feel pretty well every day, or are generally asymptomatic, as we saw, and don’t feel worse than those patients who are getting ADT alone.

Additionally, they reported that the fatigue of treatment with apalutamide was not worse than for patients receiving ADT alone. This is important because, again, fatigue has been identified as a potential problem with some of the drugs that are targeting the androgen receptor [AR] in this population. Knowing that fatigue isn’t worse is just another way for us to know that this drug is highly effective in prolonging survival but also effective in maintaining quality of life for these patients.

Elizabeth Heath, MD: Now we’re in a different space. We’re now in the metastatic castration-sensitive space, for which prior to all the new emerging data, treatment really was docetaxel based or abiraterone. The important part of the TITAN study, especially as it relates to the PRO [patient-reported outcomes] data, is we are really concerned about patients in the long term. How do they feel? What adverse effects are going on?

It’s great to say, “Here’s your medication. I’ll see you later,” but patients have to live with the adverse effects. Having the quality-of-life parameters, other facts that are measured, is important for these patients because we don’t want to just prescribe medications. We want to make sure we’re prescribing them and that they’re tolerating therapy, and that their quality of life and their impact isn’t negative. And that’s really important because sometimes, fortunately, these men are on therapy for years, and that’s what we hope for. But it can’t be at any cost. So to show that there’s really no difference compared with placebo is really important.

I’m not sure the data change much. I think it’s supportive, again. When all the data points come in and you feel as though this is what you’ve been doing, it gives you a sense of comfort that you’re on the right track and that you’re not harming the patient. But you’re getting the utility of, “Oh, wow: the survival benefit, the PFS [progression-free survival], all the things that matter to us as oncologists are still there.” Sometimes you get that but at a big cost. There are other studies that show that other drugs don’t become as standard in mainstream. But in this case, I think it’s just supportive data that make us all feel confident that we’re on the right track.

Matthew R. Smith, MD, PhD: The patient-reported outcome data from TITAN showed that patients begin the study with a relatively high, global quality of life, and that their quality of life is maintained throughout the course of the study. There are really no meaningful differences between placebo and apalutamide, which is important, and meaningful information to help understand the impact of this treatment. It appears that these well-documented benefits of improved progression-free survival and overall survival come at relatively little cost in patient quality of life. Now, it is worth mentioning that some of these measures are relatively insensitive to show subtle changes in quality of life. To get a full sense of the tolerability of therapy, one should also look at the safety information for apalutamide and any other drug in this setting.

The approval of apalutamide in metastatic castration-sensitive prostate cancer based on the results of the pivotal TITAN trial provide an additional option for patients in this really important disease state. There are differences in tolerability between agents. There are some patients who, perhaps, are not good candidates for docetaxel or abiraterone acetate plus prednisone, based on their age and comorbidities. And so apalutamide’s efficacy and safety data provide a nice option for some patients who wouldn’t be good candidates for these other treatments and, arguably, would be a good option for patients who also might be a candidate for those other therapies. As a clinician, it’s always attractive to have good, effective, and safe options, so we can provide the most benefit to the largest group of patients in this setting.

Alicia Morgans, MD, MPH: When clinicians are choosing treatments for metastatic CSPC, I think it’s important for them to have the opportunity to review the efficacy data—how well the drug works in prolonging survival—but also the patient-reported outcome data that reflects how the patients feel and how their quality of life will be. This data are really critically important when physicians have those conversations with patients about what life will be like when they choose 1 drug for treatment of this disease versus another. The information we have from TITAN suggests that quality of life is maintained and that fatigue is not worse with the treatment of mCSPC with apalutamide. This gives patients and clinicians information that they need to potentially choose this treatment or another treatment. They have the details and data that they need to make that choice.

This is also important because the FDA has recently approved this drug. And for patients, it means more options, more things to consider, more ways to find the right drug for them. Without these kinds of approvals and without this progress, patients are left to have only the drug that we have available. In this case, we have multiple drugs available with more on the horizon, likely. I think it’s an exciting and wonderful time for patients to be able to choose, again, the right drug for him and for his life, knowing both the quality-of-life data and the efficacy data.


Transcript Edited for Clarity
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