ADCs Associated With Fatigue Among Patients With Breast Cancer

ADCs Associated With Fatigue Among Patients With Breast Cancer

Researchers have found that among patients with breast cancer treated with antibody-drug conjugates (ADCs), nearly 40% experienced fatigue.

The study, findings of which were published in Critical Reviews in Oncology/Hematology, analyzed data from 7,963 patients participating in 31 studies.1 Researchers found that there was a 39.84% (95% CI, 35.09%–44.69%) incidence of all-grade fatigue during treatment via ADC monotherapy.

Researchers noted that among the 3 ADCs that have been approved by the Food and Drug Administration for the treatment of breast cancer—trastuzumab deruxtecan (Enhertu), sacituzumab govitecan (Trodelvy), and trastuzumab emtansine (Kadcyla)—fatigue is the most common side effect, with a subgroup analysis finding treatment-specific rates of ADC-induced fatigue to be 47.05% (95% CI, 42.38%–51.75%) with trastuzumab deruxtecan, 42.82% (95% CI, 34.54%–51.32%) with sacituzumab govitecan, and 35.17% (95% CI, 28.87%-41.74%) with trastuzumab emtansine. Fatigue, researchers said, was also more common with trastuzumab emtansine combination therapy than with monotherapy.

But fatigue, as nurse practitioner Jamie Carroll, APRN, CNP, MSN,of the Mayo Clinic in Rochester, Minnesota explained, is multifactorial.

“Our patients do have fatigue on antibody-drug conjugates,” said Carroll. “But I don't think that you can exactly say that fatigue is related only to our medications. So, fatigue, yes, it's related to the medications that our patients are receiving. But I also think that fatigue is related to the fact that maybe they're not sleeping well, maybe our patients are having multiple episodes of diarrhea, and they're back and forth to the bathroom [at night]. And so yes, that's related to the drug, but it's not directly related to the drug, it's related to side effects from the medications themselves.”

Carroll discussed how nurses can help patients manage fatigue and the impact unchecked fatigue can have on patient outcomes.

Whether patients are being treated with ADCs or other treatments, what are some ways that nurses can help patients manage fatigue related to their treatment?

First off, you want to make sure that you're managing all of the other side effects too—so managing their nausea, managing their diarrhea, managing their vasomotor symptoms. So, if they're having night sweats in the middle of the night that are affecting their sleep and their quality of their sleep, you want to make sure that you're managing those as well.

For fatigue, I try to get patients to make a list of the things that they want to do and the things that they have to do. And this is really hard for patients, but I try to get them to say the things that they have to do, to give those to somebody else. And so those are things that are like cleaning the bathrooms, or making dinner. Those are things that are on the list that you have to get done every day, but delegate those to somebody else.

And then the things that you want to do, like play with your kids or walk to the park, those are the things that I want you to do. So, it's really planning your day around the things that bring you joy, not the things that are on your list—because the toilets have to get cleaned, but who wants to do that? Nobody. And so really planning so that you're focused on the things that bring you joy and the things that you want to do, and so really kind of focusing on those things. Because of that, you're really better managing and keeping your energy on those things that you want to do, and so you're not expending all of your energy on the things that don't bring you joy. But I think it's really hard for many of my patients to delegate away those tasks that you know you have to do. Nobody wants to tell somebody else to clean their toilets.

How prevalent of an issue is fatigue among patients?

I think that fatigue builds on itself. I look at it as the number of lines of therapy that somebody has under their belt, if you will, the more fatigue will build over time. So, the patient that is first line metastatic, they may have more energy reserves than somebody that's been on treatment for the last couple of years, that person has had more hits to their bone marrow, and it's harder for their hemoglobin to recover and your hemoglobin is your oxygen-carrying red blood cells and your oxygen helps give you energy, too.

And so, the more lines of therapy that you've had, with that comes more clinic appointments, more traveling in the car, more hotel stays for some patients that don't live in the close vicinity of their clinic. All of it compounds. I think that those patients tend to have more fatigue [in] the later lines of therapy.

How can unchecked fatigue adversely impact patient outcomes?

Unchecked fatigue, it's that multifactorial thing too. So it's more fatigue, it's lower [blood] counts, it's side effects that continue to build, too. It's neutropenia, so lower white [blood cell] count, lower red [blood cell] count, it all compounds on each other.

I think fatigue is one of those things, it's challenging, because when they're at home, in the middle of their cycle, that's when their fatigue is going to be the worst. When they come and visit us, that's when their fatigue tends to be better, because their counts are higher, they're farther out from their last dose of treatment. And so sometimes patients don't share as bad as that last cycle was because they want to get their next cycle of chemotherapy. And I think our memories tend to be very short-lived, and so we don't remember what it was like the last three weeks, we just are looking forward to the next cycle of chemo. And the less you share with the providers, the less chance there is that you're going to have a hold or a dose reduction.

And so unchecked fatigue can lead to worse outcomes, so it's really important that patients are as upfront as possible. And so with that, I think it's also important that you journal, so that when you're with your provider at that appointment, you can look back over the course of 14, 21 days, however long your cycle is, and you can say, this is how I felt on days 1, 2, 3, 4, whatever that cycle is, so you can share those updates so that your provider can accurately dose your treatment, based on how you felt the last couple of weeks.

Reference

Zhang H, Shen G, Yang P, et al. Incidence of antibody-drug conjugate-related fatigue in patients with breast cancer: A systematic review and meta-analysis. Crit Rev Oncol Hematol. 2024;196:104292. doi:10.1016/j.critrevonc.2024.104292