Yan Emphasizes Use of Supportive Care With Dato-DXd in Breast Cancer
During a live event, Fengting Yan, MD, PhD, discussed safety outcomes from the TROPION-Breast01 and supportive care for datopotamab deruxtecan in metastatic breast cancer.
Fengting Yan, MD, PhD
Breast Medical Oncologist
Swedish Cancer Institute
Seattle, WA
Several antibody-drug conjugates have emerged as alternatives to chemotherapy in pretreated metastatic breast cancer. While relatively tolerable, they each have particular toxicities to be managed carefully, as was discussed in a recent virtual Case-Based Roundtable meeting. Fengting Yan, MD, PhD, who moderated the event that included oncologists in the Las Vegas, Nevada area, discussed adverse events of special interest and how supportive care provided early or prophylactically can mitigate them.
CASE SUMMARY
- A 44-year-old woman was diagnosed 4 years ago with grade 2 estrogen receptor–positive, progesterone receptor–positive HER2 0 by immunohistochemistry invasive ductal carcinoma, staging pT2N1; 21-gene recurrence score: 28.
- She underwent breast-conserving surgery plus sentinel lymph node biopsy followed by adjuvant chemotherapy and radiotherapy, then received leuprolide plus letrozole.
- Metastatic recurrence in bone and lung was discovered 2.5 years later on leuprolide plus letrozole (lung biopsy confirmed).
- First line: fulvestrant plus ribociclib (Kisqali) for 10 months until progressive disease was identified (no actionable alterations on tissue or circulating tumor DNA next-generation sequencing)
- Second line: capecitabine (Xeloda) for 10 months
- Now, MRI and PET/CT show new lytic and sclerotic lesions in L1-L2 vertebrae and new lung lesions(largest 2.2 cm).
- Liquid biopsy shows no actionable alterations.
What was the toxicity profile reported in the TROPION-Breast01 trial?
Yan: The rate of grade 3 [or higher] adverse events [AEs], interestingly, is way lower than chemotherapy. With chemotherapy it was 46% and with datopotamab deruxtecan [dato-DXd; Datroway], it was only 22%.1 Dose reduction is less common with dato-DXd than chemotherapy [Table1]. Dose interruption is less than chemotherapy, and there are no deaths, and looks like it’s much better tolerated. The overall safety profile was very consistent, and no late-onset toxicity was observed, [with a grade 3 or higher AE rate] of approximately half of the chemotherapy, which is nice to have. For these patients, it’s not only how long they live, but also quality of life, and so it’s reassuring to see the AEs are less common than with chemotherapy.
Nausea can be more common than with chemotherapy. Stomatitis is a highlight [51.4% any grade vs 13.1%]. Typically, I don’t like to deal with that because I don’t have a lot of treatment options. Neutropenia is less common than chemotherapy. Alopecia can happen; over 10% of patients had grade 2 alopecia, so be aware of that. Fatigue of grade 3 looks very similar to that with chemotherapy, and eye toxicity is also more common than with chemotherapy, and we need to keep that in mind. Anemia and leukopenia are less common than chemotherapy, and keratitis is more common than chemotherapy.
What AEs were of special concern and how severe were they in the trial?
Two very interesting AEs we observed during the clinical trial were oral mucositis and stomatitis. Approximately 43% of patients don’t have those AEs [Figure1]. About 26% were grade 1, and we don’t need to adjust anything. So about 30% of the patients would have grade 2 or grade 3, and grade 3 was only in 7%. That’s when it’s clinically symptomatic and requires intervention.
For the ocular toxicity, more than half, 56%, did not have those AEs [Figure1]. Approximately 32% were grade 1, and 10% were grade 2, when it’s symptomatic, and that’s when we need ophthalmology to evaluate the patient, and we may need to delay the dose. What is more interesting is that interstitial lung disease [ILD] is not as common as with T-DXd [trastuzumab deruxtecan; Enhertu]. It is very interesting to see that in 96% there’s no event and only 4% of the patients developed ILD, compared with 10% in T-DXd. There was 1 grade 5 AE, but the majority were grade 1 or grade 2.
Figure. TROPION-Breast01 TRAEs of Special Interest
Dato-DXd, datopotamab deruxtecan; ILD, interstitial lung disease; TRAE, treatment-related adverse event
The mucositis or stomatitis AEs were resolved or recovered in over 86%. The [grade 3] ocular events are resolved in 86% of the patients, too. It can happen, but in the majority of the patients, the AE can resolve.
The ocular AEs were very interesting, and the most common events were dry eye in 27%, keratitis in 24%, blepharitis and increased lacrimation in 8% of each, and meibomian gland dysfunction in 7%.2 Often, this eye toxicity, specifically keratitis, is quite common, but the patient can be scared, and that’s when I got after-hours calls, and often the patients were very anxious. The median time to onset is about 2 months [range, 0.03-23.2]. I have some patients I started on dato-DXd, and they came back for the second infusion and told me, “I have no AEs yet. I’m going to stop my eye drops. I’m going to stop my dexamethasone oral rinse.” I had to tell them, “No, I’m sorry. On average, time to onset is 2 months.” We have to continue those preventive treatments. Ocular AEs led to permanent dato-DXd discontinuation in less than 1%; it can happen, but it rarely led to discontinuation.
How do you prevent or give supportive care for these particular AEs?
The prophylaxis is important. I start everyone on the ocular AE prevention and stomatitis prevention. We make sure the patient has an eye exam. It can be ophthalmology or it can be optometry, and [should be done] prior to start of the treatment, and at least annually while on treatment or at the end of treatment, or anytime as clinically indicated. We have to make sure to give them lubricant eye drops, and I make them use them 4 times a day. What is more important is typically, we don’t recommend them to wear contact lenses. For 99% of patients, that is not a big deal, but there are a few patients who were not happy about that, so make sure they are aware of that recommendation.
Stomatitis is why I truly emphasize being proactive, because after it happens, we don’t have a lot of good treatments. We emphasize using the dexamethasone oral solution prophylactically 4 times a day, and I make sure I teach them they need to swish at least for a minute or 2 and spit it out. I ask them to hold ice chips or ice water throughout the infusion and also use a soft toothbrush and continue flossing and make sure they rinse with baking soda and salt. The oral prevention is important to prevent stomatitis and mucositis.
How do you manage these AEs when they have occurred?
For ocular adverse event management, the starting dose is one 6 mg/kg infusion every 21 days. When we need to reduce the dose, reduce to 4 mg/kg. The second dose reduction would be 3 mg/kg. After that, we would recommend discontinuing. For the eye toxicity, typically, when it’s grade 1 keratitis, the patient comes in and the eye looks slightly red, and if it’s grade 1, we can continue. But when it’s confluent superficial keratitis, when there is cornea [epithelial] defect, or they are losing more than 3 lines in best corrected visual acuity, that’s when I’m worried, and we would want to withhold the treatment until the AE resolves. After the symptoms resolved, we can choose to keep the same dose or consider dose reduction. If it’s a corneal ulcer or a stromal opacity or the best corrected distance visual acuity is only 20/200, that’s when we need to hold the treatment and we need to reduce the dose. When there is corneal perforation, we need to permanently discontinue the medication, but that was not common at all in the study.
When there are any new or worsening ocular symptoms, we want to make sure to send the patient back to the eye care professional, and we need to monitor them throughout the treatment, when we have to reduce the dose, and I will not hesitate to reduce the dose.
I typically write a note to the ophthalmologist and tell them they’re going to start this medication with ocular toxicity. There is a QR code that the ophthalmologist can scan and read, so often I found that to be helpful. We have to teach them, because this is so new, and we have to teach the ophthalmologist to make sure they understand what they are talking about.
We participated in the clinical trials, and I had a good experience on the clinical trial, but off clinical trial, my patient was one of the first nationwide I studied on dato-DXd. She had brain metastases from 2019 and leptomeningeal disease from 2021, and she’s still alive. She’s still doing great. I started her on dato-DXd from February 2025, and I made her do the eye drops and oral rinse, and she has not had AEs. She already had her staging MRIs, and she’s doing great. It’s truly an active agent, and we will need to have more experience for this medication.
DISCLOSURES: There were no known relevant disclosures.
