Datroway Slows Brain Metastases in Triple-Negative Breast Cancer

Datroway (datopotamab deruxtecan) kept cancer in the brain from growing longer than chemotherapy in patients with triple-negative breast cancer (TNBC) who had brain metastases, according to an exploratory analysis of the phase 3 TROPION-Breast02 trial presented at the 2026 ESMO Congress.

The trial compared Datroway with chemotherapy as a first treatment for patients with advanced TNBC who were not candidates for immunotherapy. Among the 61 patients who had brain metastases when they joined the trial, the cancer in the brain was controlled for a median of 9.5 months with Datroway, compared with 2.5 months with chemotherapy, according to Dr. Rebecca Dent. Five patients who received Datroway had their brain metastases disappear on scans.

In an interview with CURE, Dent, a medical oncologist at the National Cancer Centre Singapore and a professor at Duke-NUS Medical School, discussed what the findings mean for patients, why some patients cannot receive immunotherapy and which side effects to watch for.

This interview has been edited for length and clarity.

CURE: For someone with triple-negative breast cancer that has spread to the brain, what do these findings mean for their treatment options?

Dent: Up until now, we really haven’t had any data from randomized phase 3 trials showing activity in the CNS [central nervous system]. For years, we’ve known that patients with triple-negative breast cancer who have CNS metastases have a poorer outcome, and we don’t have a lot of drugs that are active. In the real world, we see about four to seven months of survival and two to three months of progression-free survival, so the amount of time they’re on a treatment.

Up until now, we’ve mostly just been giving different chemotherapies, but it really hasn’t been satisfying, because ultimately these patients do progress. And the side effects from having brain metastases are pretty tragic and really difficult for patients and their families.

So what’s really unique is to have data showing there’s some activity in the CNS and that it’s durable. Sometimes you can get a response, but do you actually get some quality of life? Do patients stay on the treatment? That’s what’s meaningful for patients. Does it give them that window where they’re not wondering if something’s responding?

Some patients can’t receive immunotherapy. Why is that, and how does Datroway give them another option?

I can imagine how it can be very confusing when you read that patients are ineligible. It can actually mean a number of things. Immunotherapy cannot be given to patients who have certain autoimmune conditions. It’s a small percentage, but immunotherapy activates the body’s own immune system, so if you have an autoimmune disease, you can get quite severe side effects.

Another reason might be that they’ve had immunotherapy in the curative setting, and where they live, it may not be approved again if they have an early relapse. Or they might be somewhere where it hasn’t been approved yet because it’s quite expensive, so it depends on the country they live in. The majority of patients in this trial were PD-L1 negative. Then there’s a small percentage who were PD-L1 positive, where normally we would give immunotherapy, but they were included because of one of these ineligible categories.

The regimen can cause side effects like mouth sores and eye problems. What should patients watch for and tell their care team about?

This compound is directed at what we call TROP2, which is highly expressed in triple-negative breast cancer, and that’s probably why it is such an active drug. But there are also TROP2 receptors in the lining of the mouth and on the surface of the eye. So when you’re really hitting your target, those are two areas where we see side effects.

For mouth sores, the first thing is prevention: a [steroid] mouthwash seems to do a good job of preventing them in the first place. What was reassuring is that on the study, nobody stopped taking the medication because of mouth sores. If patients do notice sores in their mouth, they should see their physician. They may need a break and then restart while taking the preventive mouthwash.

The eye side effects usually start as dry eye, which you can treat with lubricant drops, and we tell patients not to wear contact lenses. If it becomes quite difficult, it is important to see an eye doctor. For the majority of patients, it was mild, but in a small percentage, it was more serious, and most of those patients saw improvement once the drug was stopped or the dose was reduced. So the key thing is to make sure there’s open communication.

One really reassuring thing: For a patient who’s had chemotherapy in the curative setting and then has an early relapse, that can be very traumatizing. They’ve barely recovered from their chemotherapy, they may be tired, and their blood counts may be low. Dato-DXd [Datroway] doesn’t seem to lower blood counts as much, so there’s less risk of infection, and overall, I’m seeing a lot less fatigue. The infusion is also a lot shorter, and it’s given once every three weeks, which makes a big difference depending on where you live.

Why was it important to include patients with brain metastases in this trial?

We wanted to make this as real world as possible. So we mandated that everybody have screening of the brain, and we allowed both treated and untreated brain metastases. Treated means they had surgery or radiation, and the majority of patients in this trial had radiation. Untreated means the physician said, “These brain mets are really small, and they’re not causing symptoms. We’re going to give systemic therapy and rescan them every six weeks.” That way, we can actually observe whether this drug is active in the brain, rather than waiting to see if patients get symptoms.

This is one of the very few studies out there that includes patients with untreated brain metastases. When I started treating triple-negative breast cancer 20 years ago, up to 50% of patients would screen fail. They would get worked up for a trial and then be excluded. We would treat the brain met, but their liver and lung disease would become more aggressive, and they would never even get a chance to go on systemic therapy. So this gives us some reassurance that if brain metastases are small and not causing symptoms, we have a systemic therapy that is potentially active, and we can monitor every six weeks to make sure there’s at least some stability.

What did the analysis show?

When we looked at the median progression-free survival in the CNS, it was two and a half months for patients receiving chemotherapy and nine and a half months for patients getting Dato-DXd. That’s nine and a half months that they are going to stay on the treatment, and that’s median.

We also looked specifically at response in the brain. In patients who had evaluable disease, we had five complete responses, meaning there was no evidence of disease. Median time to response was about a month and a half. When you get a response, you hope it’s sustained, and we had one patient who was on treatment for more than two years. It’s not universal, but in patients who get a response, it does seem to be sustained. That’s meaningful for physicians and for patients, and it’s certainly not what we see in the real world.

How should treatment with Datroway be coordinated with radiation and surgery for patients with brain metastases?

One of the challenges is that every patient is a bit different. If you have a patient with really aggressive disease in the liver and lung and you’re using a drug like Dato-DXd, I think you’d be very comfortable giving them systemic therapy and monitoring the CNS disease. As long as it’s not growing, I don’t think you need to touch it.

But if that patient had very minor disease elsewhere in the body and one brain metastasis, I think you need a multidisciplinary team to discuss that, because very often, if there’s one lesion, we might want to remove it. We have also seen with ADCs [antibody-drug conjugates] that you can get radiation necrosis, so you do have to be careful how you integrate it into care. There’s no one-size-fits-all.

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