Antibody-Drug Conjugates in Breast Cancer: Strategies for Toxicity Management - Episode 6

Managing Patients With MBC on T-DXd Therapy

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Strategies used to help monitor and manage T-DXd treatment-related adverse events.

Kevin Kalinsky, MD, MS: This patient returns to clinic for follow-up, and she’s experiencing nausea and fatigue. Kandra, do you have any thoughts about some of the adverse effects that Komal mentioned, or about some of them being easier to manage than others? Do you have any thoughts about nausea and a good antiemetic regimen for when we’re starting with this agent in patients? Maybe address some of the other adverse effects that Komal mentioned, just in terms of fatigue or hair loss or anything else you’re seeing in the clinic besides the pulmonary toxicity that we’ve highlighted.

Kandra Horne, DNP, MSN, WHNP-BC: Komal did such an excellent job in describing that in great detail.There’s a patient who stands out clearly to me because she was doing great on her prior therapies. Then we placed her on T-DXd [trastuzumab deruxtecan], and she declined physically: severe fatigue, some nausea, and her counts dropped a little. She started experiencing alopecia, which was emotionally devastating for her. We dose reduced her, which was helpful as far as her being able to continue with therapy. It was so mentally and physically debilitating for the patient, she was just concerned she wasn’t going to be able to continue with the treatment. That’s 1 particular patient who stands out to me. For the most part, we need to know ahead of time that these symptoms can occur, make sure that there’s an antiemetic regimen available, talk to patients, and know how to manage adverse effects.

Kevin Kalinsky, MD, MS: As you were mentioning that case, it made me think of a case that we had in clinic. We had an older patient who had metastatic HER2 [human epidermal growth factor receptor 2]–positive disease who had large pleural effusions and was short of breath. It can be difficult if somebody has symptomatic lung issues to figure out if it is a result of the drug or the disease. Sometimes it can be a hard to distinguish. Kandra, any other clinical pearls that you have for management of T-DXd [trastuzumab deruxtecan] in clinic?

Kandra Horne, DNP, MSN, WHNP-BC: Just to make sure that we look at the patient holistically and see what their performance status is. For the most part, when we’re placing our patients on these drugs, we started at the standard dose of 5.4 mg/kg. Optimize the patient from the beginning of the treatment, and allow the patient to look for these symptoms and adverse effects, such as the ILD [interstitial lung disease], which can be symptomatic and severe to the point that they don’t minimize the cough. Be able to recognize that early on so it won’t develop into something more serious.

Kevin Kalinsky, MD, MS: Allison, Komal, any other pearls you’d like to mention? The other thing that I wanted to highlight: Komal mentioned DESTINY-Breast03, as we saw updates on these data at San Antonio [Breast Cancer Symposium]. For the small population of patients who have CNS [central nervous system] metastasis, there seems to be some clinical activity in the CNS. Are there any other clinical data or pearls that you have for providers who are utilizing this agent?

Allison Butts, PharmD, BCOP: I was going to say 1 that Kandra brought up, hair loss, because for a lot of our patients, that’s a major issue. Unfortunately, for a lot of our patients, they’re well maintained on HP [trastuzumab, pertuzumab] for quite some time. For a lot of them, this will change, but they had been on T-DM1 [trastuzumab emtansine] for quite a while and had regained their hair at that point. It can’t be overlooked how important thinning hair is for these patients. It’s a little unpredictable, as Komal said. But it’s a delayed hair loss, and it’s something we certainly need to discuss with patients for whom this might come as a surprise.

Kevin Kalinsky, MD, MS: Komal?

Komal Jhaveri, MD, FACP: I was just going to say the same thing, that I’ve learned that overpreparing a patient for alopecia goes a long way compared with not mentioning or forgetting to mention that. Fortunately, most of my patients don’t end up having it. When they do have it, sometimes the hair starts growing back, which is also very weird. They stay on therapy, but the hair is growing back. I’m still trying to understand who develops it, why they develop it, and how it comes back—that happens, but it happens less often. I haven’t had grade 2 alopecia, and fortunately I haven’t had ILD clinically in my standard-of-care practice. Those 2 have been good for us. Kandra, I’m curious about your patient with nausea who you had to dose reduce. Did that come on quickly, or was it after awhile? Was it a chronic thing that needed dose reduction?

Kandra Horne, DNP, MSN, WHNP-BC: It was fairly quickly.

Komal Jhaveri, MD, FACP: I agree that nausea has been something that I felt like has been more predominant and accurately reported as 1 of the most common adverse effects. That’s the first thing that patients report—and fatigue. In terms of a clinical pearl, here’s a quick 1: I had a very young woman with gorgeous hair, an African American woman with great locks of hair. I had scared her about alopecia to be honest, because I didn’t want her to feel shocked if it came. Fortunately, she did not have hair loss, but she progressed through at least 6 lines of therapies, most recently with neratinib and capecitabine. Tucatinib wasn’t approved at that time, and she was on a clinical trial at our institution [Memorial Sloan Kettering Cancer Center]. She had this open wound in her breast, like a breast mass, which was the main issue. The rest of her disease was OK, but that mass was uncontrollable.

We started on T-DXd [trastuzumab deruxtecan], and after the first dose, it had completely healed. It remains healed, and she remains on T-DXd [trastuzumab deruxtecan] and still has her hair. It has been very gratifying to see that she’s got a good stretch. She recently did have a little progression again in the breast, but I was able to get palliative radiation therapy to the breast, and she remains on therapy. I think it’s an active drug. We have to be vigilant about certain toxicities. Some are common, and some are rare but could be fatal. If we’re vigilant about these and support them, then it’s a great therapy.

Transcript edited for clarity.