Understanding the Risk-Benefit Comparison of Agents That May Cause ILD


Key opinion leaders share risk-benefit considerations when utilizing therapies that may increase a patient’s risk of developing ILD.


Joyce A. O’Shaughnessy, MD: With that in mind, we have a long list of agents, some higher risk than others, but they’re valuable to us. Mark, when you’re approaching a patient, whether it’s HER2-positive disease, ER-positive disease, PD-L1–positive disease, how do you think about managing and balancing the benefits, the potential benefits, and the risk? Does the risk for ILD [interstitial lung disease] make you concerned and put the treatment off a bit for the patient? How do you think through that risk and benefit discussion?

Mark D. Pegram, MD: Great question. Unfortunately, in oncology we rarely have the consideration to not treat. Some of the agents we’ve been talking about have very important efficacy data, including survival benefits and the like. We can’t put off the likes of say CDK4/6 inhibitors in ER-positive metastatic breast cancer. The key is patient education so they’re aware of what to look out for at home, when to call the office, when to insist on an early follow-up clinic visit, for example. We have a 24-hour hotline for oncology patients at my center, so training those staff so that it’s on their Rolodex of when they’re going to triage patients, page the physician on call and send them over to the emergency department vs having them come in the next day or two for clinic follow-up. That’s very important training.

All of us make use of allied health personnel in the form of nurse practitioners and physician assistants. Educating those folks is critical because they sometimes do independent visits, independent from the attending physician at academic centers at least They need to be very aware and adept at management of ILD, drug-induced ILD in particular. These are the things I would be talking about with patients. The fact is the risk of drug-induced ILD is usually lower than the risk of disease progression in the case of many patients with metastatic breast cancer. The equation falls out on the side of treatment rather than watchful waiting for most patients with breast cancer. That may not be the case for other diseases like melanoma. Sometimes you can have a watch and wait attitude there based on a solitary lung nodule that’s been resected, for example, that sort of thing. I’m thinking about patient education and staff education at all times for this condition for the drugs that frequently are associated.

Joyce A. O’Shaughnessy, MD: Yes. What I’m hearing you say, Mark, is that you treat with the best treatment you have for the patients. We increasingly thankfully have moved a lot of these effective agents into the curative setting, such as now pembrolizumab in the preoperative triple-negative breast cancer setting. Thankfully, the risk of serious pneumonitis is very low, like in the 1% to 2% range. I’m sure as we get into patients with more robust immune systems, we’re going to see more lower grade, but we have to treat anyway because this is going to cure an extra percentage of patients.

That’s my approach, too. I’ve never not utilized an agent because of concern that someone might get ILD. That’s mostly come to the fore with trastuzumab deruxtecan. My experience has been so far that I certainly haven’t seen anything that I’ve been concerned about. I have had some patients who have developed some kind of small patchy infiltrates that are a change from their CT scan that have made me worry. If it’s a tiny, little thing, I must admit I’ve chosen to just continue to treat the patient and follow them closely. With a second change now I’m referring, etc. I haven’t been, unlike with some of the other immune-related adverse events where I have had heartburn and insomnia, that has not happened with the pulmonary effects so far, checkpoint inhibitors, nor with everolimus. I haven’t seen that much everolimus-related ILD or pneumonitis in recent years. With trastuzumab deruxtecan, I just haven’t had a lot of issues, but a little bit of the transient things coming and going. It’s right, we’re using now the CDK4/6 inhibitors in the adjuvant setting. What you were saying, Mark is just vigilance, heightened awareness on the part of the patient, the family, all of our staff, ourselves, etc.

Transcript edited for clarity.

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