Extended Adjuvant Therapy in HER2-Positive Disease
Adam M. Brufsky, MD, PhD, and Lynn Acierno, BSN, RN, OCN, RN-BC, provide an overview on the use of neratinib, a targeted therapy, as extended adjuvant therapy in HER2-positive breast cancer.
PUBLISHED January 11, 2018
Adam M. Brufsky, MD, PhD: There are a few issues that can occur with extended adjuvant therapy. One of the first ones, and this is true for all therapy, really, is concerns of people going from IV to oral therapy. They come in for their IV every 3 weeks, or every week, or whatever they’re doing. Suddenly, it stops. Do people ever have a problem with the safety net of that? Are they only comfortable going on oral therapy?
Lynn Acierno, BSN, RN, OCN, RN-BC: Responses can go either way. Some people welcome the idea of taking an oral pill every day. They feel like they’re doing something every day for their cancer. There is a whole spectrum of side effects. Some of the oral drugs are a little bit more tolerable than some of the IV drugs. Some patients have told me they feel IV medicine is more potent and that they would rather get the IV.
Adam M. Brufsky, MD, PhD: Right, I’ve heard that. It’s stronger.
Lynn Acierno, BSN, RN, OCN, RN-BC: There are a lot of responses to that, and we’ve got answers for all of them.
Adam M. Brufsky, MD, PhD: Yes, I agree with you. We talk about it all the time with people. Just because your hair doesn’t fall out doesn’t mean that it isn’t good therapy.
Lynn Acierno, BSN, RN, OCN, RN-BC: Right.
Adam M. Brufsky, MD, PhD: People expect to have to suffer to beat their cancer. I think that’s something that we both try, very hard, to dispel. The therapy is the therapy. It’s going to work, or it’s not. It’s going to have side effects or it’s not. Those 2 definitely don’t relay, a lot of the time, and I think that’s an important issue to tell people about.
Lynn Acierno, BSN, RN, OCN, RN-BC: I think they realize that, again, with the treatment plan. That, they know. But if we’re making a change because of the progression, then it’s more difficult for them to understand. And, again, if they’re going on an oral pill, I’ve had patients be more concerned that it’s not…
Adam M. Brufsky, MD, PhD: It’s not as strong because it’s by mouth, I agree. It’s something that you’ve got to tell people.
Going back to neratinib, you have experience with our clinical trial patients. We did a trial, with neratinib, where we were trying to measure the amount of diarrhea that patients had from it. As you mentioned, that seems to be the biggest problem with this drug. Before we go to diarrhea, is there anything else that patients have had with this drug, in your experience? Rash?
Lynn Acierno, BSN, RN, OCN, RN-BC: Again, fatigue is one. It can be overwhelming. It can be a debilitating fatigue. For diarrhea, I understand there’s actually a prophylactic, which you start the day of your first…
Adam M. Brufsky, MD, PhD: Right, around-the-clock antidiarrheals. Right.
Lynn Acierno, BSN, RN, OCN, RN-BC: I don’t have enough experience to draw on, with neratinib.
Adam M. Brufsky, MD, PhD: It’s a fairly new drug. But we have a lot of experience, for example, with lapatinib [Tykerb] in our practice. It used to be the same thing, but the differences now with Tykerb are that we reduce the dose very quickly. Everybody starts with 5 pills. Then, we’ll reduce to 2 or 3 or 4 pills, or whatever, within a few weeks. But with neratinib, you really have to be very careful. I tell people that, up front, and I’m sure you do. When people come in, we say, “You are probably going to need antidiarrheals for at least the first month. It’s going to have to be around-the-clock.” Again, it’s not an explosive diarrhea. It’s more that you have to go to the bathroom all the time. We have school teachers who are concerned about this.
Lynn Acierno, BSN, RN, OCN, RN-BC: Yes, that’s a concern.
Adam M. Brufsky, MD, PhD: The kids are all laughing because the teacher has to go to the bathroom all the time. It’s sad. You’ve got a bunch of fifth graders and they’re laughing because their teacher has diarrhea. You don’t want to be in that scenario. I think that’s a big thing. People have to understand that they have to be on antidiarrheals for a long time. That’s how we prepare patients for that.
Lynn Acierno, BSN, RN, OCN, RN-BC: Well, informed consent. We try to let them know everything that may or may not happen. We tell them, “If this isn’t something you think is going to work with your lifestyle, we may need to look around.”
Adam M. Brufsky, MD, PhD: Exactly. But again, that’s the tension between kind of breaking up with us and deciding to go on and finish their cancer issue or to be on something that may help (but it is going to potentially cramp their lifestyle). That’s always going to be the tension with this. We do have ways around it, though. I do think this is something that will help people out.
As you said before, informed consent is really important. This means that we all try, in our clinic, to tell people up front what’s going to happen as best as we can. As we said before, not everybody is the same. We try to give them a potential worst-case scenario. “You’re going to be on antidiarrheals for a month. You may have to go the bathroom a lot.” We try to think about scenarios: if you’re going on a long car trip or you’re in a big meeting.
Lynn Acierno, BSN, RN, OCN, RN-BC: Or, again, your occupation.
Adam M. Brufsky, MD, PhD: Your occupation. And again, we try to work around what their occupation is. We look at what they do and ask, “Is this right for you?” A lot of people are game to try. And if people are scared, you say, “Listen, try it. You can always stop it. It goes away.”
The key, though, is really being proactive up front. You need to tell people exactly what they’re going to need in terms of antidiarrheals. You need to prepare them with how much we think it is going to happen and what to do if they get diarrhea, such as when to call, when not to call, etc. I think it’s important.
Lynn Acierno, BSN, RN, OCN, RN-BC: Right. We’ve had many patients hospitalized because of diarrhea.
Adam M. Brufsky, MD, PhD: We have. That happens, occasionally, and we have to let people know that. And again, as you said before, we always are open for fluids. People need to come in and get fluids. And during that time, you kind of work on their diarrhea and make sense of it.
Lynn Acierno, BSN, RN, OCN, RN-BC: As nurses, we really encourage patients to push fluids. It could be anything that melts. It doesn’t have to be water.
Adam M. Brufsky, MD, PhD: Right. It doesn’t have to be water.
Lynn Acierno, BSN, RN, OCN, RN-BC: We encourage that they always have something beside them that they’re drinking. It could beGatorade, soups, or anything that melts.
Adam M. Brufsky, MD, PhD: I agree, anything that melts.
Lynn Acierno, BSN, RN, OCN, RN-BC: Hopefully, as neratinib becomes more popular, perhaps there will be more research or we’ll have even better treatments. We’ll learn more.
Adam M. Brufsky, MD, PhD: There is a trial, going on right now, that we’re a part of. We put a few people on it. In people who are getting neratinib as extended adjuvant therapy, they’re actually looking at the degree of diarrhea when we give them prophylactic therapy up front. It’s kind of the follow up study to the one that was already done. And so, we’re trying to figure that out, to see what the true incidence of diarrhea is in people who get this prophylaxis.
At the end of the day, this drug seems to be fairly effective. Again, we’re talking about a 3% to 5% absolute improvement in recurrence rates, going up to as high as 95%. That’s pretty good. But on the other hand, there is diarrhea. It’s always a risk-benefit ratio. It sounds like any diarrhea really happens for the first month or two. But for a lot of people, the diarrhea tends to go away or be ameliorated with dose modifications.
Lynn Acierno, BSN, RN, OCN, RN-BC: It is. It’s usually just an issue in that first month.
Adam M. Brufsky, MD, PhD: It’s rare to have someone have it for a really long time. Generally, a lot of it goes away. We also consider tachyphylaxis. It’s something that people need to think about. Again, it’s not for everybody. In my practice, we’re going to recommend this for people who really are at high risk of recurrence. We are going to recommend it for somebody who doesn’t have a complete pathologic response to their TCHP [docetaxel, carboplatin, trastuzumab, and pertuzumab]. We are going to recommend it to somebody who maybe has a lot of lymph nodes, up front, where you really want to do more. These are people that hopefully will be a little more motivated to stay with us and want to continue for that extra year. It sounds like it’s a big deal, but it’s manageable. We’re doing it for people who are at a higher risk of recurrence.