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Managing Metabolic Aberrations and CV Events from ADT

Insights From: Dipti Gupta, MD, MPH, Memorial Sloan Kettering Cancer Center; Susan Slovin, MD, PhD, Memorial Sloan Kettering Cancer Center
Published: Wednesday, May 30, 2018



Transcript: 

Dipti Gupta, MD, MPH: I talked about the increased rates of obesity, insulin resistance, diabetes, hyperlipidemia, and metabolic syndrome. ADT has a similar effect on cardiovascular disease (CVD). Dr. Slovin has shown us a lot of data—not only through the metabolic aberration pathway would you expect more cardiovascular disease, you would also expect it through the biologic mechanisms and the direct effects on plaque stability that I talked about a little while ago. The problem is that large, randomized, controlled trials are lacking, and the existing evidence regarding CVD morbidity and mortality for patients receiving androgen deprivation therapy is rather controversial.

Data from observational studies do indicate a positive relationship between ADT and CVD, but we really, really need some prospectively designed studies that don’t just look at this in a post hoc analysis but actually target looking at these cardiometabolic parameters. I’m not going to rehash the data that Dr. Slovin has already shown us, but I do want to touch upon a recent large, observational, Swedish trial of over 41,000 men with prostate cancer on ADT versus an age-matched prostate cancer–free comparison group. This showed a 21% increased CVD risk in men on GnRH (gonadotropin-releasing hormone) agonists, as compared with a control group.

In terms of timing, we’ve talked about timing for metabolic aberrations to occur, which doesn’t seem to take very long. The theme has been repeated with cardiovascular disease, where we see that the CVD risk is highest in the first 6 months. The patients who have already had a cardiovascular event or 2 within the year prior to starting therapy are at particularly high risk. These are going to really be high-risk patients—the older patients, the patients who already have cardiovascular disease or have poorly controlled or poorly managed cardiovascular and metabolic issues.

As Dr. Slovin had pointed out for us, there was an advisory that was put out by American Heart Association in collaboration with specialty organizations in 2010. In this panel, the bigger stake was held by urologists and oncologists, and I thought the document did a really good job of summarizing the literature, highlighting the risk of androgen deprivation therapy and the inconsistencies in the data that we’ve been talking about throughout this broadcast. It also made some astute observations regarding health maintenance and primary and secondary prevention.

However, it was a summary statement that was somewhat surprising to a lot of us who take care of patients. It says that despite ADT’s metabolic effects and a potential for increased cardiovascular risk, there is no clear indication for patients to be referred to internists, endocrinologists, or cardiologists for evaluation before initiation of ADT. In the current model of cancer care, is it wrong to assume that the oncologist is willing or able to act as an internist, cardiologist, and a subspecialist to take care of these very, very complex issues in patients? What do you think about that, Dr. Slovin?

Susan Slovin, MD, PhD: I agree with you completely. We’ve become chief, cook, and bottle washer. It’s really important that multidisciplinary care be ongoing.

Dipti Gupta, MD, MPH: Yes, absolutely.

Transcript Edited for Clarity 
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Transcript: 

Dipti Gupta, MD, MPH: I talked about the increased rates of obesity, insulin resistance, diabetes, hyperlipidemia, and metabolic syndrome. ADT has a similar effect on cardiovascular disease (CVD). Dr. Slovin has shown us a lot of data—not only through the metabolic aberration pathway would you expect more cardiovascular disease, you would also expect it through the biologic mechanisms and the direct effects on plaque stability that I talked about a little while ago. The problem is that large, randomized, controlled trials are lacking, and the existing evidence regarding CVD morbidity and mortality for patients receiving androgen deprivation therapy is rather controversial.

Data from observational studies do indicate a positive relationship between ADT and CVD, but we really, really need some prospectively designed studies that don’t just look at this in a post hoc analysis but actually target looking at these cardiometabolic parameters. I’m not going to rehash the data that Dr. Slovin has already shown us, but I do want to touch upon a recent large, observational, Swedish trial of over 41,000 men with prostate cancer on ADT versus an age-matched prostate cancer–free comparison group. This showed a 21% increased CVD risk in men on GnRH (gonadotropin-releasing hormone) agonists, as compared with a control group.

In terms of timing, we’ve talked about timing for metabolic aberrations to occur, which doesn’t seem to take very long. The theme has been repeated with cardiovascular disease, where we see that the CVD risk is highest in the first 6 months. The patients who have already had a cardiovascular event or 2 within the year prior to starting therapy are at particularly high risk. These are going to really be high-risk patients—the older patients, the patients who already have cardiovascular disease or have poorly controlled or poorly managed cardiovascular and metabolic issues.

As Dr. Slovin had pointed out for us, there was an advisory that was put out by American Heart Association in collaboration with specialty organizations in 2010. In this panel, the bigger stake was held by urologists and oncologists, and I thought the document did a really good job of summarizing the literature, highlighting the risk of androgen deprivation therapy and the inconsistencies in the data that we’ve been talking about throughout this broadcast. It also made some astute observations regarding health maintenance and primary and secondary prevention.

However, it was a summary statement that was somewhat surprising to a lot of us who take care of patients. It says that despite ADT’s metabolic effects and a potential for increased cardiovascular risk, there is no clear indication for patients to be referred to internists, endocrinologists, or cardiologists for evaluation before initiation of ADT. In the current model of cancer care, is it wrong to assume that the oncologist is willing or able to act as an internist, cardiologist, and a subspecialist to take care of these very, very complex issues in patients? What do you think about that, Dr. Slovin?

Susan Slovin, MD, PhD: I agree with you completely. We’ve become chief, cook, and bottle washer. It’s really important that multidisciplinary care be ongoing.

Dipti Gupta, MD, MPH: Yes, absolutely.

Transcript Edited for Clarity 
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