An Overview of Interstitial Lung Disease


Joyce A. O’Shaughnessy, MD, provides an overview of interstitial lung disease, considering both causes and possible risk factors.


Joyce A. O’Shaughnessy, MD: Hello, I’m Joyce O’Shaughnessy from Baylor University Medical Center, Texas Oncology, and US Oncology in Dallas, Texas. It is my pleasure to be part of a roundtable discussion today about treatment-related interstitial lung disease. This promises to be interesting and highly educational because this is something that we medical oncologists have had to come up to speed about, and we’re seeing this very frequently in the clinic. It’s a bit challenging, so we have some experts here today to have some very good conversation around this. I am very pleased to be joined by 2 of my colleagues; Dr Mark Pegram, who is an endowed professor of medicine and oncology at Stanford University [Palo Alto, California], and Stanford [Women’s Cancer Center]. Very good to see you again, Mark, and to be talking to you today. I’m also joined by Dr Charles Powell, who is system chief at Mount Sinai’s Pulmonary, Critical Care and Sleep Services, and the CEO of the [Mount Sinai-National Jewish Health] Respiratory Institute at the Icahn School of Medicine at Mount Sinai in New York. Very good to be here with you today, Charles.

Charles A. Powell, MD, MBA: Thanks very much. It’s great to be here.

Joyce A. O’Shaughnessy, MD: We’ve got a series of topics that we’re going to touch on and then have dialogue about, but what I’m going to do is lead off with some general comments about interstitial lung disease. For example, what is it? How common is it? Where does it occur in the context of cancer therapy? This is something I find to be quite complex because there are so many different causes of lung infiltrates. There are so many different things in our patients that can impinge upon their pulmonary function, upon pulmonary symptoms, and upon their imaging, from radiation changes to pulmonary emboli, to hypersensitivity reactions, to chronic aspiration, etc. It’s really challenging to figure out who has lung injury from one of our therapies. And then our therapies don’t always cause the same kind of lung injury by any means. There’s a variety of different mechanisms of lung injury. Interstitial lung disease—we’re going to hear from our experts here—but in terms of a definition, it looks to be a clinical constellation of symptoms, with patients having cough, dyspnea, low-grade fever, fatigue. That’s coupled with, but not always coupled with, you can find isolated imaging findings as well of ground glass infiltrates, septal thickening, subpleural nodules, etc, and that seems to be a clinical heads up that this patient may have something going on that may be interstitial lung disease related to therapy.

There are so many of our therapies that can cause lung injury. I’ve been at this long enough, I think I’ve seen 1 or more of everything, from the simple doxorubicin and cyclophosphamide that we use every day to the more notorious bleomycin and mitomycin C. So many of our targeted agents cause lung injury, pulmonary injury, such as bevacizumab, for example, or everolimus, or even trastuzumab from time to time. Trastuzumab deruxtecan, trastuzumab emtansine also can cause it. So many of the targeted agents from the EGFR inhibitors, myriad TKIs [tyrosine kinase inhibitors]. It’s a very, very long list. This has come to the fore mostly in the breast cancer arena with the checkpoint inhibitors, with everolimus, and then most recently with trastuzumab deruxtecan. The incidence of lung injury with chemotherapy agents such as doxorubicin, cyclophosphamide is quite low. It’s less than 5% of our patients. When we start getting into everolimus, for example, we’re more in the 10% range of patients having pneumonitis. With the checkpoint inhibitors, serious pneumonitis is in the 2% range, and any grade might be again less than 10%. With regard to trastuzumab deruxtecan, so far the data we have are in a very heavily pretreated population. We’ll talk more about this. It’s in the 15% range, most of it low grade, but again we’re going to see how those data evolve as we get data about trastuzumab deruxtecan in earlier lines of HER2-positive breast cancer.

I’ll mention one more thing, risk factors. In my research, I’m looking at risk factors, for example, trastuzumab deruxtecan and other of our agents, and a history of interstitial lung disease can predispose patients to another incident, so that’s something we’ve got to watch out for. Patients of Japanese origin have a higher risk. For trastuzumab deruxtecan, having had very heavy pretreatment, more than 10 lines of metastatic therapy, was a risk factor. But I couldn’t find a whole lot else that really raised the risk.

Transcript edited for clarity.

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