HER2+ Breast Cancer: Special Challenges and Expert Insight - Episode 8

Management of ILD in HER2+ BC

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Expert panelists react to polling questions and give their input on the management both symptomatic and asymptomatic interstitial lung disease in HER2+ breast cancer, also touching on this impact in the era of COVID-19.

Adam Brufsky, MD, PhD: How have you guys managed this? Have any of you seen ILD [interstitial lung disease] at all in your practice? I’ll start with Sara. Have you seen ILD in anybody?

Sara A. Hurvitz, MD: No, I haven’t. I’ve done a lot of clinical trials with this agent but have never seen ILD. I’m fortunate with that. I’ve seen it a lot with everolimus and even immune therapy, but have had the luck to not encounter it here.

Adam Brufsky, MD, PhD: Neil, how about you? Have you seen this at all yet in any patients?

Neil Iyengar, MD: I have. Unfortunately, I had a patient on the phase 2 study who was 1 of the patients who developed ILD and then died. It was very challenging because she was responding to the therapy beautifully. This was a woman who had diffuse skin metastases and terrible quality of life because she was scratching all day. We put her on trial, and she responded beautifully to this drug. All her skin lesions resolved. Unfortunately, she became mildly symptomatic with a cough. Following protocol, we immediately stopped the drug and brought her into the hospital. Unfortunately, she progressed very rapidly despite systemic steroids and immunosuppressive agents. Pulmonary was treating her with things like cyclosporin. Unfortunately, we weren’t successful in reversing this. Adam, your point about being very cautious when you see something on the scan even if they’re asymptomatic: I couldn’t underscore the importance of that statement more.

Adam Brufsky, MD, PhD: VK, are you the same way?

Vijayakrishna Gadi, MD PhD: I’m very cautious. I’ve been very lucky, like Sara, not to have had ILD happen as a result of this agent in a patient, but I have seen it with the TKIs [tyrosine kinase inhibitors] and immunotherapy agents on and off protocol. I’ve got a healthy respect for ILD as a problem that we now face for our patients. Fortunately, we’ve been able to manage it successfully.

I will say, though, the world has changed in 2019, 2020, and now part of 2021, with about 10% of humanity having been exposed to COVID-19. If this is the case, even if they asymptomatically have some lung injury, are we putting patients at a new kind of risk when we investigate how this drug works? It’s a new world. Not that I won’t use it, but my index of suspicion for these things is suddenly very high, which is appropriate for all of us to have.

Adam Brufsky, MD, PhD: I agree. We’re going to have people with asymptomatic lung damage from COVID-19 that we didn’t know about that we’re going to pick up when they walk in the door. A lot of them are going to walk in the door now because they haven’t been treated for a year. They’ve been too scared to come in and see us. They’re going to present with de novo or advanced disease and probably have some sort of coronavirus pattern in their lungs, or maybe an asymptomatic thing that we don’t know about. It’s going to be a real challenge to start treating them with these agents.

I’ll ask the last question before we’re done. We’re almost finished. This has been really great. I have a ton of questions for you guys that we won’t get to because we’ve used the whole hour. One question is: Would you treat somebody with lung disease agents? Specifically, would you treat someone with interstitial spread? Let’s start with Sara. Would you treat someone with interstitial spread with trastuzumab deruxtecan if you had nothing left?

Sara A. Hurvitz, MD: Actually, I would. We have data from a 2018 San Antonio [Breast Cancer Symposium] poster regarding all patients who were treated with this drug in phase 1 studies looking at factors associated with the development of ILD. Asian ancestry in more heavily pretreated patients were at higher doses of the agent—doses we don’t use—and were associated with more risk. But the presence of pulmonary metastases was not a risk factor. They didn’t look specifically at lymphangitic carcinomatosis in the lungs. However, patients who have lymphangitic carcinomatosis have such a poor survival that you need an active agent there. I wouldn’t hesitate to use it in somebody who’s been treated with other agents and is in that kind of trouble.

Adam Brufsky, MD, PhD: Great. Neil, any extra on that? Would you do it?

Neil Iyengar, MD: Yes, I agree. I might look to the PFTs [pulmonary function tests] to help inform that decision. If somebody is really restricted by their lymphangitic carcinomatosis, then I might have some pause. Because in that situation, that asymptomatic schmutz may actually have very significant clinical ramifications. But I agree with Sara. You really want to try to get a response in the lungs, and using an active agent in this setting may be very helpful.

Adam Brufsky, MD, PhD: VK, do you have any other thoughts on this?

Vijayakrishna Gadi, MD PhD: Yes, if a patient has this as the main cause of their shortness of breath, I’m happy to use it because you’re likely to get a good response and improve that. If it’s a patient who’s a 1-pack-a-day smoker on 3 nebulizer treatment and an inhaler and takes chronic steroids for their COPD [chronic obstructive pulmonary disease], all of a sudden I’m feeling a little different about this. The patient factors are going to also dictate how comfortable I am using this drug in that type of disease pattern.

Transcript edited for clarity.