HER2+ Breast Cancer: Special Challenges and Expert Insight - Episode 7

Monitoring Symptoms of ILD in HER2+ Breast Cancer

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Experts discuss the careful monitoring of potential interstitial lung disease symptoms, how they proceed if symptoms progress, and how they handle this in patients who are asymptomatic.

Adam Brufsky, MD, PhD: Let me talk about this case, and then we can discuss how to manage it. This patient gets T-DM1 [trastuzumab emtansine] and has liver progression, as we talked about. We start her on trastuzumab deruxtecan. This is actually a case of mine. She responds, but in her right lower lobe, she has an inflammatory infiltrate. It’s like 2x2. It’s like a random thing you always see and you’ve always blown off. I talk to her about it and she says, “Yes, I’ve been having a dry cough the last week or 2.” What do you do? It’s not like flaming ILD [interstitial lung disease], where she has the interstitial pattern on her lungs, you’re worried, and you’re calling the pulmonologist. It’s a woman who’s responding to the drug, who’s asymptomatic but has a weird thing that the radiologist would usually call “could be inflammatory.” What would you do here? Neil, how would you manage this?

Neil Iyengar, MD: This is a tough 1. In grade 1 ILD, you could consider initiating steroids. In the case that you just outlined for a fairly asymptomatic patient, if it was a new dry cough, I would be worried about it. In this situation where she’s responding and is borderline asymptomatic with this new incidental radiographic finding, my approach would be to monitor very closely, repeat imaging probably by 1 week later, and have our staff on top of communicating with her in regard to her symptoms. If the ILD is truly related to the drug, it can progress rapidly, so I have a very low threshold. If the nurse called her the next day or the third day and she’s saying that her cough is getting a little more prominent, I would hold the drug and think about starting steroids in that situation.

Adam Brufsky, MD, PhD: Sara, what are your thoughts?

Sara A. Hurvitz, MD: With grade 1, I stop therapy. In the case of an asymptomatic CT chest scan showing some fluffy infiltrates, in today’s time, I’m checking for COVID-19, of course. I’d hold the therapy and repeat the scan in 28 days. I’d have them see a pulmonologist. If the scan shows resolution at 28 days, then I’ll resume therapy. If it takes longer than 28 days to show resolution, then I won’t resume until it’s resolved then drop the dose level –1. That’s how most of the studies with this drug are being run to try to mitigate that rapid progression that can occur and can lead to death.

Adam Brufsky, MD, PhD: Yes. VK, it’s really important to stress to people that, even with the asymptomatic thing on the CT, you’ve got to stop. That’s grade 1. If it’s symptomatic grade 2, you stop forever, right? Is that how it works? What are your thoughts on this?

Vijayakrishna Gadi, MD PhD: Your patient is the kind who probably got a little too far in the trial. For example, you’re a doctor on this trial. You’ve had a patient who’s seen 7 lines of therapy and nothing is working. All of a sudden you put them on this magical drug and things are getting better and the patient says, “I’ve got a little cough,” or there’s a little thing on their skin. You say, “Don’t worry about it. It’s good. Your cancer is responding.” But these are exactly the cases we have to be on high alert.

I like the idea of pumping the brakes, reevaluating, maybe getting my colleagues from pulmonary involved, and working it up. If it’s getting better with or without steroids on its own, I’m open to trying again. If it’s not, then there’s a low threshold to move onto the next thing and get this managed, as if it were a true event of pneumonitis. I’m echoing what our colleagues have said, but this is the kind of patient who worries me. When it’s grade 2 and you know what it is, you’re going to hit it hard. This is the 1 that scares me.

Adam Brufsky, MD, PhD: Right. That’s kind of what I’m doing. She had a vacation coming up, so I told her that we’re just going to hold it. I even thought about giving her a Medrol Dosepak to try to make it go away. It’s nothing really serious. She’s on whatever the dose is now. There’s some treatment for it that we do. The important thing to stress to the audience is that if it’s an asymptomatic or minimally symptomatic patient like this, you really have to be careful. It’s not just symptomatic. There actually are asymptomatic patients.

It’s really important to know that because this can progress. You have to be very careful. We’re all going to be in the situation where it’s going to be the sixth, seventh, or eighth line of therapy, and they’re going to respond, yet they’re going to have this and you don’t know what it is. You’re hoping it’s not ILD because you want to keep treating her, but you may not be able to. That’s a really important thing to say.

Transcript edited for clarity.