Advantages of Oral Therapy for Metastatic Breast Cancer


Adam M. Brufsky, MD, PhD: We should probably turn for the next 20 minutes of this presentation to talk about delivery because ADCs [antibody-drug conjugates] are just 1 form of delivery. Something that has become pretty important over the last many years in breast cancer is that we are trying—at least I am in my practice at the University of Pittsburg Medical Center, Hillman Cancer Center, and women appreciate it—to stay on all oral therapy.

I am curious to hear your thoughts about this mainly because, the perfect example is now the CDK4/6 [cycline-dependent kinases 4 and 6] inhibitors. You have someone on a CDK4/6 inhibitor for 2 years, 3 years, or 4 years. They are used to being on it, and then all of a sudden, they progress. Then you try out alpelisib or everolimus with some other antihormonal therapy. You are then 2, 3 regimens into it, and it is now time for some sort of cytotoxic chemotherapy.

The default for all of us has been capecitabine because you are used to it, and the patients want to do it. Patients are now coming to me and they think that they are in big trouble. They get depressed, and they say, “Dr Brufsky, I have got to go on IV [intravenous] therapy now. Is this the end? Should I be talking to my family about hospice?” I am curious to hear your thoughts about this. Is that where we are going, toward trying to keep oral agents as long as we can? Is that something you guys consider? Go ahead, Lee. You go first.

Lee S. Schwartzberg, MD, FACP: I have the same experience you do, Adam. It is disconcerting for a patient with HR+ [hormone receptor-positive] breast cancer who has been doing well for 2, 3, or 4 years on oral therapies, or even if they have to come in for fulvestrant. It is not that much, but they do not have hair loss, they do not have neuropathy, and they do not have neutropenia. It is tough for them when they hear that their cancer is getting worse, and they are now going to have to go to IV therapy as well.

That is a big inducement for capecitabine. If we assume that, since we do not have the biomarkers, patients are going to do as well with capecitabine as they would with other single agents, even though we know taxanes and anthracyclines probably have the most activity of single agents, at least in nonexposed patients. The idea to that is this: you are not going to lose your hair, and you are not going to get really sick. In fact, it is just your hands and feet that we have to worry about. We can modulate the dose. We can do that remotely. You can call me in 10 days if you are having a problem. I can look at it on your cell phone and say, “Yes, let's adjust the dose.” They like that; it gives them a bit more empowerment, and it keeps them free. It is not that, “I am getting near the end. I am now coming to the clinic every 3 weeks for IV chemotherapy.”

Adam M. Brufsky, MD, PhD: George, what do you think?

George W. Sledge Jr., MD:When we at Stanford Cancer Center studied this, I was co-author on a paper several years ago that was looking at patient preferences in the metastatic setting. What we discovered, of course, is that patients differ considerably in terms of what sort of therapies they are willing to accept. It is a trade-off between toxicity and benefit. In general, patients are more focused on the benefit than they are on toxicity, particularly in younger women, our studies showed.

The younger you were, the more likely you were to accept significant toxicity for even fairly modest benefits in terms of treatment. At the end of the day, patients want to live longer first and foremost, of course. Secondly, they want to live well. Thirdly, this gets to both of your points, they would like to spend as much time with their family and friends and as little time in the hospital as possible. As much as we think that we bond with our patients, my patients would by far rather be with their spouse than with me, depending on the spouse of course.

One of the huge advantages of oral therapy is that it significantly cuts down on what has been called time toxicity. A wonderful paper I saw recently looked at how much time patients with metastatic breast cancer spent attached to the health care system. If you are an average patient with metastatic breast cancer, something like 10% of your waking hours are spent attached to the healthcare system in some way, shape, or form. That time toxicity is huge.

It is increased if you have to come in; it is not just that you are spending an hour or hour and a half sitting in the chair getting an infusion. You may have to drive a couple of hours. You have to pay a parking fee. You have to walk in. You have to wait at the reception area. You have to get a blood count. Then, you sit in the chair. Then you wait a while longer after that. Then you have to go back and get to your car. You probably had a doctor’s visit that day because it is common for us to attach those to IV treatment days. Before you know it, you have burned through a fair amount of your day. The great advantage of oral therapeutics is that they minimize time toxicity to a significant degree.

Lee S. Schwartzberg, MD, FACP: We at West Cancer Center & Research Institute did a study years ago in the context of long-acting growth factors and in both white blood cell and red blood cell growth factors. It was a time motion study that showed exactly what George is talking about with the amount of time that not only the patient by the way, but the caregiver in many cases as well, had to spend just coming to the office. Whether you are in an urban environment and have to get on a subway or if you live 100 miles away as many of the patients do around Memphis, it is a huge amount of time, with the waiting and then everything.

Doctors look through it in the filter of 15 minutes with the patient, which is not so bad, and then they go up to infusion. We do not realize that it is 3 or more hours there. It is a big deal, and it impacts their lifestyle. It is hard to work, and it can sometimes be their caregiver who it also affects. It is huge, particularly for disadvantaged populations, which we have a lot of, unfortunately, as well. It is difficult; they often do not have transportation, so they sometimes have to take 3 buses or wait for the special Uber driver who is contracted to come get them.

Adam M. Brufsky, MD, PhD: That is an interesting idea. You have an Uber driver that you contract with to bring patients into the clinic?

Lee S. Schwartzberg, MD, FACP: Yes.

Adam M. Brufsky, MD, PhD: That is cool. I never thought of that. How do you pay for that, is it through a foundation or something?

Lee S. Schwartzberg, MD, FACP: We did it with Lyft. We had a grant for it.

Adam M. Brufsky, MD, PhD: That is great. That is a good idea. That is pretty cool.

Transcript Edited for Clarity

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