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Future Management of HR+ Metastatic Breast Cancer

Insights From: Debu Tripathy, MD, MD Anderson Cancer Center; Sara Hurvitz, MD, UCLA Jonsson Comprehensive Cancer Center; Hatem Soliman, MD, H. Lee Moffitt Cancer Center & Research Institute
Published: Wednesday, Aug 29, 2018



Transcript: 

Debu Tripathy, MD: I think CDK inhibitors and endocrine options have changed how we treat patients. We have more flexibility in endocrine partners, and CDK inhibitors for the most part, I think, are very helpful as they delay progression. It does leave a lot of dilemmas, however, in what to do after seeing progression on CDK. We just don’t have much experience on how these patients do. These drugs have been recently approved. There’s 3 of them now available and it’s all happened in a very short period of time. We’re 3 years into the first approval and most patients now are being treated in the first-line setting. So, we don’t know how they respond to other drugs. How well do they respond to everolimus? We don’t even know that even though everolimus is indicated in second-line therapy.

So, we need to learn much more about what is the best option for patients afterwards. And we’re now just starting to learn from the basic science side what are some of the markers that predict who’s going to respond better to the CDK inhibitors. We really haven’t had that until now. And there’s a few candidates now who have been discovered in the last year or so. They need to be validated and then we need to decide how we’re going to incorporate that into decision making. So, I do think there’s still a lot more that we’re going to learn about how to optimally manage these patients.

Hatem Soliman, MD: The landscape of managing hormone receptor–positive, HER2-negative breast cancer is going to be influx and changing and evolving for quite some time. This is because there are a lot of new agents that are in the pipeline that are looking to change, in essence, the natural history of the disease, so that we could potentially manage it as a chronic disease for a very long time by targeting various pathways. There may be acquired resistance mechanisms or other methods that we can use in order to keep a patient from having resistance emerge or progression occur for very long periods of time.

The landscape in general is including novel therapies such as oral SERDs, which I mentioned earlier. I think they could be potential game changers in the therapy of women with hormone receptor–positive breast cancer because this class of drug is very effective but has been limited by our ability to dose it with current formulations such as fulvestrant. And so, the oral formulations will allow us to overcome some of those limitations and pharmacokinetics in dosing to deliver potentially greater efficacy to those patients, particularly in the first lines of therapy, similar to the settings for using fulvestrant that we discussed.

I do think that, in essence, what we are going to be looking at though is due to the plethora of agents that will be coming on the scene, sequencing and how to select from the vast menu of new agents that will be coming online to treat patients will become critical, so that we can best personalize our therapeutic choices for our patients. So, trials such as PACE that are looking at understanding whether or not we can continue CDK4/6 inhibition through progression and just by switching the endocrine backbone may provide additional therapeutic benefit for those patients over time, which is going to be critical. I think additional adjuvant studies now, too, are going to be very important and could cure many more women with hormone receptor–positive breast cancer who will never have to see a metastatic relapse.
 
So, trials like MONARCH-E or PALLAS are eagerly awaited to see if those results are positive, so that we can further improve our curative outcomes as well. That could have an effect though on the nature of the disease that may relapse through those treatments, and so it will be increasingly important for us to really understand what makes those tumors tick and how to overcome acquired resistance in those scenarios, so that we can continue to provide the best therapeutic outcomes for our patients over time.

Sara Hurvitz, MD: Although we’ve come a long way with the treatment of hormone receptor–positive metastatic breast cancer, it is the number 1 cancer killer for women with breast cancer, it’s the most common type and resistance is the rule. We are not seeing patients cured. I think the future’s going to be very important in terms of us beginning to define how to use real-time information about the patient’s tumor, be it through cell-free DNA or serial biopsies, to give us an idea of what’s actually happening within the tumor that’s allowing the tumor to escape our treatment.

It may be that we have to use a cocktail of therapies up front to circumvent resistance. Appropriately sequencing these agents is going to be informed by a better understanding of what’s personally happening in that tumor for that patient. So, we have a lot of work to do. We also have areas of unmet need, namely patients who develop brain metastases because it does happen here. So, I think looking at drugs that cross the blood-brain barrier, for example, abemaciclib, is going to be very important. And helping to find treatments that are going to make patients live longer and maybe even be cured.

Transcript Edited for Clarity 
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Transcript: 

Debu Tripathy, MD: I think CDK inhibitors and endocrine options have changed how we treat patients. We have more flexibility in endocrine partners, and CDK inhibitors for the most part, I think, are very helpful as they delay progression. It does leave a lot of dilemmas, however, in what to do after seeing progression on CDK. We just don’t have much experience on how these patients do. These drugs have been recently approved. There’s 3 of them now available and it’s all happened in a very short period of time. We’re 3 years into the first approval and most patients now are being treated in the first-line setting. So, we don’t know how they respond to other drugs. How well do they respond to everolimus? We don’t even know that even though everolimus is indicated in second-line therapy.

So, we need to learn much more about what is the best option for patients afterwards. And we’re now just starting to learn from the basic science side what are some of the markers that predict who’s going to respond better to the CDK inhibitors. We really haven’t had that until now. And there’s a few candidates now who have been discovered in the last year or so. They need to be validated and then we need to decide how we’re going to incorporate that into decision making. So, I do think there’s still a lot more that we’re going to learn about how to optimally manage these patients.

Hatem Soliman, MD: The landscape of managing hormone receptor–positive, HER2-negative breast cancer is going to be influx and changing and evolving for quite some time. This is because there are a lot of new agents that are in the pipeline that are looking to change, in essence, the natural history of the disease, so that we could potentially manage it as a chronic disease for a very long time by targeting various pathways. There may be acquired resistance mechanisms or other methods that we can use in order to keep a patient from having resistance emerge or progression occur for very long periods of time.

The landscape in general is including novel therapies such as oral SERDs, which I mentioned earlier. I think they could be potential game changers in the therapy of women with hormone receptor–positive breast cancer because this class of drug is very effective but has been limited by our ability to dose it with current formulations such as fulvestrant. And so, the oral formulations will allow us to overcome some of those limitations and pharmacokinetics in dosing to deliver potentially greater efficacy to those patients, particularly in the first lines of therapy, similar to the settings for using fulvestrant that we discussed.

I do think that, in essence, what we are going to be looking at though is due to the plethora of agents that will be coming on the scene, sequencing and how to select from the vast menu of new agents that will be coming online to treat patients will become critical, so that we can best personalize our therapeutic choices for our patients. So, trials such as PACE that are looking at understanding whether or not we can continue CDK4/6 inhibition through progression and just by switching the endocrine backbone may provide additional therapeutic benefit for those patients over time, which is going to be critical. I think additional adjuvant studies now, too, are going to be very important and could cure many more women with hormone receptor–positive breast cancer who will never have to see a metastatic relapse.
 
So, trials like MONARCH-E or PALLAS are eagerly awaited to see if those results are positive, so that we can further improve our curative outcomes as well. That could have an effect though on the nature of the disease that may relapse through those treatments, and so it will be increasingly important for us to really understand what makes those tumors tick and how to overcome acquired resistance in those scenarios, so that we can continue to provide the best therapeutic outcomes for our patients over time.

Sara Hurvitz, MD: Although we’ve come a long way with the treatment of hormone receptor–positive metastatic breast cancer, it is the number 1 cancer killer for women with breast cancer, it’s the most common type and resistance is the rule. We are not seeing patients cured. I think the future’s going to be very important in terms of us beginning to define how to use real-time information about the patient’s tumor, be it through cell-free DNA or serial biopsies, to give us an idea of what’s actually happening within the tumor that’s allowing the tumor to escape our treatment.

It may be that we have to use a cocktail of therapies up front to circumvent resistance. Appropriately sequencing these agents is going to be informed by a better understanding of what’s personally happening in that tumor for that patient. So, we have a lot of work to do. We also have areas of unmet need, namely patients who develop brain metastases because it does happen here. So, I think looking at drugs that cross the blood-brain barrier, for example, abemaciclib, is going to be very important. And helping to find treatments that are going to make patients live longer and maybe even be cured.

Transcript Edited for Clarity 
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Miami Breast Cancer Conference®: Attendee Tumor Board OnlineNov 30, 20181.5
Community Practice Connections™: 1st Annual Paris Breast Cancer Conference™Dec 31, 20181.5
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