A broad review of strategies to manage interstitial lung disease, including steroid use, therapy cessation/rechallenging, and dose reduction.
Joyce A. O’Shaughnessy, MD: A key question is how and when to use the steroids? I don’t think we’re necessarily all that expert about what to use, when to use, how long to use, dose to use, etc.
Charles A. Powell, MD, MBA: Yes. The principles that we’ve outlined are spot on, and they do differ depending upon the drug. To take a couple of these issues one by one, one issue we should talk about is rechallenge. If the patient doesn’t have other agents available that have similar or better likelihood of achieving a therapeutic result, then the impetus to rechallenge is that much higher. If the patient has asymptomatic or even a symptomatic pneumonitis that improved or resolved better, then the shared decision-making visit may result in a decision to rechallenge, and that would be appropriate. But if there are other drugs in other drug classes available, then it may be prudent to make a switch.
The other point is, what about steroids, when do you use them? That depends in part upon the agent. As we discussed in lung toxicity related to osimertinib, there’s no need to introduce steroids for patients who have abnormal radiographic imaging because in many patients it’s going to resolve on its own over time. Some drugs such as trastuzumab deruxtecan have a history of being associated with the incidence of progression to severe ILD [interstitial lung disease] that’s grade 4 or grade 5. Then one will be more ready to use steroids earlier in the process, which is why recommendations now exist to consider steroids even in asymptomatic patients who are exposed to trastuzumab deruxtecan. The principles of treatment with steroids are the same principles that we use for managing interstitial lung disease in patients regardless of the cost. The most common pattern that we see is an organizing pneumonia pattern. That can be caused by drugs, it can be caused by exposure to other infectious agents that we may or may not have been able to identify, or to other antigens that we are exposed to in the environment. The principle is we treat with a dose of steroids. In asymptomatic patients, this could be 0.5 mg/kg or up to 1 mg/kg, and usually it takes a few weeks of treatment to get an effect, anywhere from 2 to 4 weeks.
Then the other principle of management, especially for organizing pneumonia, is once the expected result is achieved with the initial dose, the taper needs to be slow because organizing pneumonia can recur. And one of the associations for increased risk of recurrence is a rapid taper. The taper is over the course of several weeks. Those are the principles of management as they relate to steroids for organizing pneumonia in particular, and it also applies to other types of ILD associated with drug-related pneumonitis.
Joyce A. O’Shaughnessy, MD: Could I ask you, Charles, with the checkpoint inhibitors, I’m very used to a very slow wean. You really have to go slow. When it comes to trastuzumab deruxtecan or some of our CDK4/6 inhibitors, can we wean a little more quickly, or not necessarily?
Charles A. Powell, MD, MBA: We prefer to go slow and steady, and continuously monitor patients’ symptoms and then to have the similar cadence of imaging studies to confirm improvement to resolution. We prefer not to go quickly.
Joyce A. O’Shaughnessy, MD: Over 6 to 8 weeks?
Charles A. Powell, MD, MBA: Typically.
Joyce A. O’Shaughnessy, MD: We’re all very anxious; if somebody has a grade 1 ILD and they’re on trastuzumab deruxtecan, it’s a very effective agent, a lot of times these patients are heavily pretreated. They don’t have a whole lot of other good options. We’re anxious to get back, and particularly if there was just a little bit of change on the imaging. You said it takes 2 to 4 weeks to get a result in terms of symptoms. When is it reasonable, like to repeat a scan after 4 weeks? Remember, if it resolves quickly then we can go ahead at the same dose, etc.
Mark D. Pegram, MD: According to the prescribing information, it says to look again on day 28. That would be the time for reassessment to look and see if there’s resolution because if there is, you could resume at the same dose. That may be another reason to consider early intervention with steroids, just to optimize the probability that you’ll be able to stay relatively on schedule without long waits.
Charles A. Powell, MD, MBA: Yes, I concur. It’s different for different drugs, and we have detailed management algorithms for drugs such as trastuzumab deruxtecan. One can schedule the steroid dose, the taper, and the imaging schedule around those management guidelines to potentially allow patients to resume at the same dose, or with a dose reduction, or for us to learn that the drug may need to be discontinued.
Transcript edited for clarity.