Out-of-Pocket Can Mean Cancer Meds Are Out

Kathy D. Miller, MD; Dawn L. Hershman, MD


February 22, 2016

This feature requires the newest version of Flash. You can download it here.

Kathy D. Miller, MD: Hi. I'm Kathy Miller, professor of medicine at the Indiana University School of Medicine in Indianapolis, Indiana. Welcome to Medscape Oncology Insights, coming to you from the 2015 San Antonio Breast Cancer Symposium (SABCS).

New therapies and agents are emerging in breast cancer, making this a very exciting time for our field and our patients. But those anticancer agents can't work if patients can't or won't take them, and that means we need to think about toxicity and the cost of therapy and how they may impact adherence. More and more attention has been given to patient-reported outcomes and quality of life, and the finances associated with adherence.

Here to talk about these important issues is a friend and colleague, Dr Dawn Hershman, who is professor of medicine and epidemiology and director of the Breast Cancer Program of the Herbert Irving Comprehensive Cancer Center at Columbia University in New York, New York. Welcome, Dawn.

Dawn L. Hershman, MD: Thank you.

It's Cancer; Of Course Your Patients Will Take Their Meds

Dr Miller: Let's talk first about some terminology. We talk a lot about compliance and adherence. I think to the nonepidemiologist, those terms mean the same thing, but they are not exactly the same. What is the difference?

Dr Hershman: In general, there are two different ways of measuring adherence.

There are patients who take their medications, but take them irregularly [nonadherent]. They forget when they have to refill their prescription. Maybe a month or two goes by and they start again, or they take it for a couple of days and then they stop taking it for a couple of days.

Then there are patients who stop altogether. They are done. They are not going to take it anymore. The patients who stop we consider nonpersistent. The patients who are taking it intermittently are noncompliant [or nonadherent].

We say that if a patient is taking their medication 80% of the time, that is pretty good. We are pretty happy with that, and we know that taking a medicine 80% of the time pretty much has the same effects as taking it 100% of the time. But when you start to get less than 80%, that is when the effects of the medications really start to diminish.

Dr Miller: Now, this not just an issue in cancer therapy, but I am often surprised when I mention this to colleagues who treat diabetes, hypertension, or other chronic illnesses. They often assume [that because] it's cancer, of course your patients take their medicine. Do they?

Dr Hershman: A lot of the research that has been done in noncompliance focused on HIV, diabetes, and other conditions. You are absolutely right; people just assume that if it is cancer and it can kill you, people will take their medication.

When we and others first started to look at this issue around hormonal therapy for breast cancer, we were shocked to see that only about 50% of patients finished the 5 years exactly as prescribed.[1] About 25% of patients stop early, and about 25% of patients take it intermittently.

When you have to take a therapy for 5 years—every day—and you don't have any symptoms, after a couple of years pass, you start to lose motivation.

Even though we know that these medications have a huge effect—the most important effect for some women in terms of reducing their risk for breast cancer coming back—we know that some of the factors that really can contribute to that are related to knowing the medicine works. A lot of patients don't really understand how the medicines work and why they work, and that can be a big influence on taking it. When you have to take a therapy for 5 years—every day—and you don't have any symptoms, after a couple of years pass, you start to lose motivation.

Dr Miller: You also don't have "any sign from the gods" that this is working—which is perhaps a bit different from hypertension or diabetes, where you can measure blood pressure and blood glucose. You can see a difference if you are taking the pills or not. Whether seeing a difference motivates you might be a different story, but at least there is a way of knowing it is having an effect, and we don't have that.

Dr Hershman: You are 100% correct. You have no blood pressure or hemoglobin A1c to monitor, no viral load, so women [with breast cancer who are taking hormonal therapy] need to have faith. They have to really understand the research and why they are taking it, because these medicines have side effects. Here, they are taking something that causes side effects and interferes with their quality of life, hoping that their cancer won't come back. I think it is very difficult to take something that causes side effects when you don't have any proof that it is working.

Out-of-Pocket Costs a Barrier to Adherence

Dr Miller: We have to talk about another barrier to continuing therapy, which means we have to talk about cost—which, I think for many of us, is still an uncomfortable subject to talk about, and one about which we often are not so well informed.

We may not understand what a big difference small changes in out-of-pocket costs might make.

I think many of us probably don't ask patients what their out-of-pocket costs are, and we may not understand what a big difference small changes in out-of-pocket costs might make. I remember a study that you were involved with that looked at the aromatase inhibitors as they became generic, so the out-of-pocket cost changed.[2] What is the difference with different levels of copays?

Dr Hershman: We first looked at this issue with hormonal therapy and found that small differences, such as going from $30 to $90 out of pocket, can have a dramatic effect on staying on the medication as well as what we call "medication possession ratio" or being adherent 80% of the time.

It was actually one of the things that persisted, no matter how we looked at the data. It is a really big issue when medications cost a lot, because the more the medication costs, the more out-of-pocket costs are incurred by the patient. There can be tremendous variability with that. We had a natural experiment when the aromatase inhibitors went generic, because for many people's insurance, they went from having to pay $90 a month to not having to pay anything. We saw a dramatic improvement in adherence when the medications became generic.

Through a variety of different studies we have been able to look at things such as income.[3,4,5] A patient's income has a big effect on their likelihood of being adherent. Their wealth—not just how much they are making, but their overall wealth—has a big effect. We start to think, if cost has such a big effect for hormonal therapies when the out-of-pocket costs are still pretty low, [then how much greater will the effect be for high-cost medications?] Even at its peak, a month of Arimidex® (anastrozole) cost maybe $350. Now we have medications that cost $10,000 a month.

Dr Miller: That is the most amazing thing—that we have come to a world where you could actually say with a straight face, without batting an eye, that $350 out of pocket per month is pretty cheap. That's amazing, because if I were paying that out of my pocket, it would feel like real money. I would think twice about that.

Are you going to feed your family? Are you going to pay your rent? Or are you going to pay money for medications when you don't have any symptoms?

Dr Hershman: Most people, as I said, can't afford $30 or $90 a month. If you are on a fixed income and you have to be on these medications a long time, you have to make real choices about how you are going to spend your money. Are you going to feed your family? Are you going to pay your rent? Or are you going to pay money for medications when you don't have any symptoms? These choices are very difficult for people to make, and it really makes us question our healthcare system when you have medications that cure people, that reduce the risk that they are going to die of metastatic breast cancer, and we can't provide patients with those medications.

Dr Miller: Do we know whether oncologists are aware of this? Are we asking our patients about these issues?

Dr Hershman: Yes, I think people are becoming more aware. When I think of the SABCS meeting a couple of years ago, maybe you would see one presentation at most on this issue. This year, there may be six posters in the discussion session and multiple posters in the poster session looking at this issue.

There is a lot more research in this area, both in terms of understanding it and in trying to think of interventions to improve it. We have made a lot of progress, but I think physicians generally feel uncomfortable. They feel that they are going to make the patients feel bad. But the research out there suggests that patients want to have these discussions so they know what their options are.[6,7]

Side Effects of Oral Therapies Take Their Toll

Dr Miller: I want to turn our last few minutes to some of the toxicities, because that is another big issue for patients—many of whom with early-stage disease are cured of their cancer with our therapies, but they may live with the long-term side effects for a very long time.

With oral therapies, side effects could certainly impact their willingness to stick with the medicine, but with some of our intravenous therapies, side effects may also impact their ability to keep on the medicine; that has been particularly a concern with human epidermal growth factor receptor 2 (HER2)-targeted therapies and with heart function.[8,9,10] I think we were all comforted that with trastuzumab, even with an anthracycline-containing regimen, the rates of heart failure were quite low—less than 4%[8]—but that is not 0%, and in a curative population, that is potentially devastating. There was a fascinating study presented here, the MANTICORE trial,[11] which looked at a potential intervention to reduce that risk for heart failure.

Dr Hershman: I think with all clinical trials, we enroll a very selected patient population, such as patients with no comorbid diseases and patients whom we think will do well long-term. But then, when we start to give these medicines to our patients in clinic, we are dealing with an older patient population, patients on other medications, and patients with risk factors, who would have never been included in the clinical trials, and you see these rates of long-term effects being much greater than are reported in clinical trials.

I think such is the case with some of these agents that affect the heart, especially when given in combination, and so there has been a big interest in trying to figure out ways of protecting the heart. There is a lot of interest in beta-blockers and angiotensin-converting enzyme (ACE) inhibitors because we know from the cardiovascular literature that they can improve remodeling and they certainly help prevent patients with a history of myocardial infarction from developing heart failure.

Protecting the Heart From Breast Cancer Therapies

Dr Hershman: The MANTICORE trial[11] was a very interesting study that was reported at this meeting. It randomized women that were starting trastuzumab (Herceptin®) to get a placebo, a beta-blocker, or an ACE inhibitor and looked to see, over the course of the year, whether or not these agents protected against heart dysfunction.

The rates, as you said, are very low. So they looked at a surrogate, MRI, and their primary endpoint was looking at change in end diastolic volume. They didn't see a significant difference among the three arms in terms of their primary endpoint, but they did see a real difference in terms of the change in the ejection fraction. It's the change in the ejection fraction that we use, as clinicians, to help guide us with therapy. I think eight patients in the placebo arm ended up having to have a change in their therapy—either a dose reduction or a delay, because of this change in ejection fraction—whereas the other two groups didn't have any [change in therapy].

This is the first suggestion that medications may actually help prevent toxicity from a therapy.

This is the first step. There is a lot of interest, and luckily, a lot of other randomized trials that are going on have bigger cohorts and are looking for a longer period of time. These will help guide us. But this is the first suggestion that medications may actually help prevent toxicity from a therapy and may help patients in other ways as well.

I think we have to figure out who the right patients are, what the right endpoints are for these studies, whether these changes are clinically meaningful, whether patients would have improved on their own, and which patients are really at the highest risk for this toxicity for whom we need to intervene. It is certainly not an intervention we want to do for everybody.

Dr Miller: It also seems like a study where discussion with our patient advocates could be really instructive. Even though many of us in the scientific community looked at the very low rates of heart failure and felt like the benefits far outweighed those risks, I remember a different interpretation and a different weighting of those issues in many patients who saw that heart failure risk as much bigger and saw the tradeoffs to be in a different direction.

Dr Hershman: Yes; I think you are absolutely right, because we know that about 15% of high-risk patients who really should get chemotherapy don't, and one of the main reasons is fear of side effects and long-term consequences of treatment. It is interesting because in the study, only 20% of patients got an anthracycline-containing regimen—which really increases the heart failure risk—so the majority of these women got regimens with Herceptin (trastuzumab) without an anthracycline, and we still saw differences.

I think that for patients, we need to listen to the issues that are important to them to get them the treatment they need and not overtreat them and put them at risks unnecessarily.

Dr Miller: Dawn, it has been a pleasure.

Dr Hershman: Thank you.

Dr Miller: These are incredibly important issues to think about. Not only taking translational science from the laboratory to the clinic, but to the clinic to our patients in the community—and that means we are going to have to tackle the issues of adherence, cost, and toxicity. I am excited to see that getting a greater focus.

Thank you to our audience for joining us. This is Dr Kathy Miller, from the San Antonio Breast Cancer Symposium 2015.

In response to a question from Medscape, Dr Hershman provided this expanded definition of the terms "adherence" and "compliance": "There are several terms for underuse of hormone therapy in breast cancer. A patient can be nonpersistent, which is a way of saying she stopped the medication early. A patient can be nonadherent, which means she is taking the medication less than 80% of the time. "Noncompliance" is a way of describing either of these. Often, these terms are used interchangeably."


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.