Sara A. Hurvitz, MD

We’re getting ready to close this out in the next 10 minutes. One of the next things that we want to discuss is how cancer treatment has changed during the COVID-19 era. It’s really interesting. In the beginning, back in March and April [of 2020] when everything shut down, we remained open, but we opened up video visits and telehealth, which previously was not really something we were able to do. It’s fascinating to me that things that we thought we couldn’t do because of legal implications and HIPAA [Health Insurance Portability and Accountability Act] concerns, all of sudden—within a month—all the lawyers and everybody figured out how to make it happen. Now we have telehealth and video visits available to us, which has made it great for patients who haven’t wanted to leave the home.

There’s been a lot more uptake of the use of oral therapies, and subcutaneous Herceptin and Perjeta and home health visits have become more common to keep people out of doctor’s offices. Can you describe how things changed for you, how your perception of going into the office changed, and what your experience was during this crazy pandemic?

 In the beginning, I was really frightened that I would get COVID-19. Remember when we were wiping off our groceries and you felt like it was everywhere? It was super easy to catch it, and I knew with my compromised lungs, it would be a very serious situation. I had that fear. I’m 59 [years old], and I’ve never had my government tell me so many different things that contradict each other. I was born in the 1960s, we have public health together. It’s like, “What happened?” That was really scary.

It’s great to be on the oral medication, and now I’m on the Herceptin that you get at home. That was also great. I have to go in for my blood work and Xeloda. I feel sad when I see patients who are getting a heavier chemotherapy [regimen]. They can’t have a loved one with them, and I feel like it’s hard for them. I also see it’s a burden for the nurses who are great about it but have to do much more emotional labor of comforting and calming people, which in my experience, would have been handled by my husband, my friend or my sister. I also see that everybody’s being extremely careful and extremely thoughtful. I’m aware of it, but less frightened about getting it than I was.

Yes, and hopefully everybody will be vaccinated shortly. In the next month, there’s a move, at least out here in Los Angeles, to start vaccinating patients who have chronic conditions. We need to get the vaccine into everybody.

Let’s now look to the future. This is a quite exciting time in the field of HER2 [human epidermal growth factor receptor 2]-positive breast cancer treatment. There are a number of new agents, in addition to the ones that have all been approved very recently. We have a number of new targeted therapies and lots of clinical trials. At UCLA [University of California, Los Angeles Health], we have five or six clinical trials that are looking at new drugs that target HER2. It’s a very exciting time. Moreover, a lot of these therapies, like tucatinib and TDXd [trastuzumab deruxtecan], are being looked at in early stage disease, so the curative setting; stage 1, 2 and 3. We may be seeing these drugs move up into earlier-line settings, our goal being to prevent metastatic occurrences from even happening. I think that in the next five years we’re going to even see bigger changes occur.

There are also a number of drugs that are looking at how to best treat patients who have brain metastases. Fortunately, you do not. The hope is that the tucatinib is providing you a layer of protection, so that you avoid that from happening. But we do have a number of agents being looked at in clinical trials to deal with that when that happens as well.

In my own practice, I’m using tucatinib in patients who have had at least two prior lines of therapy in the metastatic setting. I’m using it just like I’m using it in Caitlin, but we also have a clinical trial where tucatinib is being combined with TDM1 [trastuzumab emtansine] in patients in the first- or second-line setting to see if that’s a safe and active combination.

It’s a really exciting time. I see nothing but hope ahead of us. I know Caitlin has her goals of good quality of life and keeping the disease at bay, but my goal would be that she live out a long life and die of something totally different at the age of 95.

I like that. By then, you will have found a cure to that problem, too. I might never get out of here.

How do these advances make you feel? Have you been keeping track of all the changes in this field?

 You always tell me there are so many more things. I had never heard the word armamentarium, and I love that word. It’s a great word. You would always say there’s more and more, and more things are being approved, so I’ve always had a upbeat feeing that it won’t be like, “Well, we only have one thing to try, and then you’re going to be in bad shape.” I feel like, “OK, there’s a fight to be fought. There are things out there.”

That’s great. In closing, can you give some sage advice to patients who may find themselves in your shoes at this point? What would you say to them?

 As having metastatic recurrence? I would just say that in our minds, and with most other cancers, with stage 4, there’s no stage 5. That’s the end. That’s the scary one. That’s the metastatic disease. But it’s not that way for us. We can treat it for a long time as a chronic disease, and we all know people with chronic diseases. Their lives are more challenging, whether it’s diabetes, fibromyalgia, or one of those things. But it’s not unusual for someone to have a chronic illness that they’re managing all the time. When I think of it that way, then my terror goes away altogether. And, until I hear otherwise, I am going to think of it that way.

That’s an amazing way to end. Very hopeful.

Videos

Caitlin Flanagan, a patient with HER2+ metastatic breast cancer, and Sara A. Hurvitz, M.D., discuss treatment approaches and modifications during the COVID-19 pandemic.

Treating HER2+ Metastatic Breast Cancer During the COVID-19 Pandemic

Have you had any difficulty remembering to take your pills or adhering to it? Are there any tricks that you’ve found, because you’re having to do pills twice a day?

 I don’t have any tricks, but I need some tricks. I need to get a pill box and put them in. Because they have to be in separate pill boxes—it had said not to put the two pills together in a pill box for some reason—I never got around to it. I’ve definitely had times when it’s 11 at night and I’d think, “I have to get up and eat some bread and take that medicine,” because I’d forget it.

Right. That’s something, I’m lucky enough to have nurse practitioners in my practice who are able to help with teaching patients. You’re a veteran patient, so maybe you didn’t get as much coaching from them, and that would be bad on us. To assume that you don’t need coaching when you’re going on a new regimen is not proper on the clinician’s side. I do think patient education and making sure you bring in your medications to appointments is important. Sometimes we’ll have patients bring in their bottles so that we can count and see, and make sure they are where they should be, if they have too many pills left, etc. When you’re not on a clinical trial and we’re not managing pills at that level, adherence to the medication can certainly affect outcome.

 It was very scary to have it at home. It was like, “I’m responsible?” I was used to going to the suite, infusion, nurses and blood work. I didn’t have to actively do anything except show up for my appointments. So it was a little anxiety-producing that the chemotherapy drugs are here in my house. It’s not like an antibiotic you have to take. You have to stay with that. That was an adjustment, but a wonderful adjustment, too, because you’re not in the infusion suite all the time and being reminded of your situation that way.

Right. To go over the side effects a little bit with this particular regimen, tucatinib, capecitabine, which is the oral chemotherapy drug known as Xeloda, and trastuzumab are given together as a triplet therapy. The trastuzumab is IV [given intravenously] every three weeks, but the pills are given twice a day. It can be a little confusing because the Xeloda is given two weeks on, one week off, where the tucatinib is given continuously. It is a bit tricky. The side effects, based on the clinical trial evidence we’ve seen, can include diarrhea, as Caitlin described. Everyone needs to be coached to have Imodium on hand at home and to call if it’s getting really bothersome. Fatigue is very common. Even though it’s oral and not making hair fall out, it does make people feel tired. Some people can get dry, cracked palms and soles or mouth sores from the Xeloda.

It’s important to be seen every three weeks in the beginning, every month at least, and have blood work done. Occasionally, patients can have their liver enzymes go up. That’s not liver failure per se, but abnormalities in that, so that needs to be followed as well. But in the scheme of all the regimens we give, this is one of the better tolerated ones. I tend to start with a lower dose of the Xeloda and titrate up, rather than starting at the level that we’re supposed to get to.

 That would have been very depressing to start that high.

Yes, I didn’t want you to run away screaming after the first cycle.

Caitlin Flanagan, a patient with HER2+ metastatic breast cancer, discusses the learning curve of taking an oral medication, tucatinib, in combination with chemotherapy, and Sara A. Hurvitz, M.D., reviews methods for medication adherence.

Adhering to Oral Therapy for HER2+ Metastatic Breast Cancer

What side effects have you been experiencing? How are you tolerating this regimen?

 I don’t know which to ascribe to which medication, because I’m on the Xeloda. Is the Xeloda the tucatinib?

No, Xeloda is capecitabine. So Xeloda is the chemotherapy.

 Capecitabine, right. I’ve had diarrhea, but it’s manageable with Imodium. I’m super tired, but my friends always say, “Well, we’re 59 [years old].” I always say, “Well, I’m 59 with treatment.” So that doesn’t go well. I do feel tired and I pace myself, but I don’t know how much is from having 18 years of treatment. I might feel tired from that. It’s the pandemic. Everybody’s tired and grouchy. So I don’t know, but it’s very livable.

Has it affected your ability to write, do your work, family life, any of that?

OK. What about your emotions and mental well-being with all of this?

 That’s not very heavy on me because I had that long 10-year time of no progression. And now, there are all these medications. I’m not very troubled. I’m not saying I can’t get super scared super fast if we find something, but I feel like I can go from zero to 100, as you know, very quickly, so I don’t feel like I need to preload my anxiety. I’ll be able to get a full case of anxiety if we get a bad result at some point. But, no, I’m not super anxious right now.

How do you define success in terms of treatment?

 It’s two things. It’s being able to live life on my own terms, defined by me, as long as I can, and with manageable or negligible side effects. That, to me, is success. It’s not so much about what the cancer load is at any one moment. It’s like, “OK, is it stable? Am I alive? Am I able to go for a swim or whatever?” To me, that’s success.

Those are very reasonable and realistic goals. Have you talked to anyone about goals of care in your cancer journey?

Your husband or health care workers or anyone?

 People don’t like to hear about that, outside of people who are used to it. People in my life don’t want to hear that. But I have people; I have a therapist, I have you. There are people in the cancer world who I can talk to about it. But the people who love you just want to think you are cured, you’re being cured, everything is fine. To be totally honest, it might frighten me if they’re like, “Yes, we need to get ready for this eventual occurrence.” It’s nice to have people seeing me looking well and feeling well and not seeing me as marginalized.

Right. Have you felt supported on the clinic side? Of course, I’m asking you, so of course….

 I’m a good complainer, I would say. Dealing with the pandemic and the telemedicine and all that is really good. It’s not that private, concierge level of a small private practice in Beverly Hills, but I’d more than happily substitute a larger system. Actually, UCLA [University of California, Los Angeles Health] works really well, I have to say. It’s just big. But I love being able to look at my own results in my chart, contact you and contact the nurses. Everybody’s been really great, starting with you on down, saying that quality of life is important as well. You’re not saying, “Don’t bother me, I’m saving your life now,” or whatever the appropriate way of saying that mean thing would be.

Caitlin Flanagan, a patient with HER2+ metastatic breast cancer, discusses how her quality of life has been since she began taking tucatinib with chemotherapy.

Tucatinib With Chemotherapy for HER2+ Metastatic Breast Cancer

There have been a number of advances since we first met. Trastuzumab was FDA-approved for advanced, or stage 4, breast cancer in 1998. Then lapatinib was approved in 2007, so it took almost 10 years for a second HER2 [human epidermal growth factor receptor 2]-targeted therapy to be approved. In 2012 and 2013, we had 2 more agents. Then, as we jump to 2019 and 2020, we have a slew of new approvals. It is an exciting time, but it also can be a bit of a confusing time for clinicians who are treating stage 4 breast cancer because there are so many options.

We now always start in the metastatic setting with a taxane, like you got, and trastuzumab, and we combine it with pertuzumab. If you were diagnosed today with stage 4, that would be the regimen, which is pretty similar to what you had. As the second-line therapy, the standard of care is TDM1 [trastuzumab emtansine], which is what you received. The toxicity you experienced was quite significant, which is why we took you off of it. Not everybody has that experience, but you experienced significant toxicities from it. If I’m recalling correctly, it was neuropathy, nausea, and your liver wasn’t happy.

So we switched you to the trastuzumab/pertuzumab and endocrine therapy since you’re triple-positive. Your tumor has estrogen receptors, as well as the HER2. That worked for a good long time.

But now, in the third-line setting and beyond, we have all of these therapies from which to choose. How to sequence them is tricky, because we don’t have any clinical trials saying, “If you do this one third and this one fourth, and this one fifth, patients will live longer than if you do it in this reverse order,” so we have to use the side effect profile and what we know about the drug’s activity. Some of these drugs penetrate the blood-brain barrier and actually prevent brain metastases or delay the presentation of brain metastases. About 30% to 50% of patients with HER2-positive breast cancer can develop brain metastases, so this is a huge area of unmet need, and that’s really exciting that we have agents that do that now.

Then, we have another drug like TDM1. It really packs a punch. It’s a very active therapy, but it has side effects associated with it like pneumonitis, which is inflammation of the lungs. We wouldn’t want to give it to somebody who has underlying issues with their lungs, like pulmonary fibrosis or a history of pneumonitis.

We use a lot of individual patient factors—where the disease is, how healthy the patient is, what other problems the patient has in their medical world, diabetes, high blood pressure, heart disease—to help us decide. Then, of course, we factor in the patient’s goals; as you stated, goals of wanting to be alive as long as possible, but also measured against the side effect profile of each of these agents.

In my own practice, after TDM1, I will use either tucatinib/capecitabine/trastuzumab, which was FDA-approved last year in 2020, or I will use TDXd [trastuzumab deruxtecan], which is the antibody-drug conjugate. For you, I was concerned about the toxicity of the TDXd, given how hard TDM1 was for you. You didn’t have a huge disease burden at your time of progression, so I didn’t feel like I needed to give you something that was really tough that was going to knock the disease back. And the data regarding tucatinib are quite phenomenal. It’s been shown to not only lengthen the time a woman can live with this disease without it being out of control, but it also improves survival, and it improves survival in patients with active brain metastases—it may be providing protection there. That’s why I made that recommendation.

But when I first told you about the regimen, do you recall our conversation or what I told you about the drugs?

 I had a scan after having my numbers going up. Then you called and said, “We need to talk today.” I thought, “Uh-oh.” You said I could come in or call, and I called. You were like, “OK, great. It’s Sara. I’m in the room, and Maddie’s in the room,” and I thought, “Oh, this is really scary.“

But then it wasn’t that scary because you said very gently, “Well, there are some nuances in the scan. We should treat these nuances, but nothing’s really bad or terrible right now.” You started going through all the different things, but I remembered the one, I think it was the first one you mentioned, about the brain. My whole life is reading and writing. I’m a writer. I’m sure everybody is most terrified of brain metastases. But everything about it frightens me, like not being considered compos mentis to make any end-of-life decisions. I’m really afraid of brain metastases.

When you had said that this one was particularly made, or that was a particular feature, I thought, “That one sounds good. What do you think?” You said, “Yes, I think that’s why I said that first, because that would be a good choice.”

Sara A. Hurvitz, M.D., reviews the advances in HER2+ metastatic breast cancer that have been made over the past decade.

Sara A. Hurvitz, MD

Treating HER2+ Metastatic Breast Cancer During the COVID-19 Pandemic

Adhering to Oral Therapy for HER2+ Metastatic Breast Cancer

Tucatinib With Chemotherapy for HER2+ Metastatic Breast Cancer

Advances in HER2+ Metastatic Breast Cancer

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