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Welcome to CME on ReachMD. This episode is part of our MinuteCE curriculum.
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Dr. Yu:
This is CME on ReachMD, and I'm Dr. Helena Yu, a medical oncologist at Memorial Sloan Kettering in New York, New York.
Dr. Jänne:
And I'm Dr. Pasi Jänne, also a medical oncologist, from the Dana-Farber Cancer Institute in Boston.
Dr. Yu:
Monitoring and managing the adverse events we encounter with HER3-directed antibody-drug conjugate therapy does require interprofessional collaboration as well as some former knowledge of the potential adverse events with these ADCs.
Pasi, have you had a patient with interstitial lung disease or pneumonitis on HER3-DXd? And maybe you could describe the case and tell me how you managed it.
Dr. Jänne:
Yes, I have seen both grade 1 interstitial lung disease, which would be asymptomatic CT scan-only finding and then symptomatic interstitial lung disease or what was felt to be interstitial lung disease as well. So I think it's important that if someone presents with symptoms, breathing difficulties, cough, etc., that imaging is obtained to try to understand could this potentially be interstitial lung disease and also to rule out other potential causes of findings if such are seen on the CT scan, such as an active infection, congestive heart failure, as some potential examples. And oftentimes we do involve our pulmonary colleagues in this situation as a patient may need a diagnostic bronchoscopy. We may involve our cardiology colleagues for cardiac evaluation or an echocardiogram to rule those causes in or out.
And assuming nothing else is found, and this is felt to be drug-related interstitial lung disease, then treatment often involves corticosteroids for a period of time with close monitoring, patient's clinical status, O2 saturations, and ultimately follow-up imaging to show that it's hopefully disappeared. In general for grade 1, which are CT scan only, we have not been treating those individuals, but rather, as was done in the trials, hold treatment for some period of time, 3 to 6 weeks, and then re-image to hopefully show disappearance of those findings within the potential ability to re-treat individual.
Dr. Yu:
Yeah, I think that with our targeted therapies, our immunotherapies, many different cancer therapies causing pneumonitis, I think we do have some familiarity with how to manage this. I think one thing to explicitly say is that obviously if there's any concern for interstitial lung disease, that holding therapy is sort of first and foremost –
Dr. Jänne:
The right thing.
Dr. Yu:
– as we kind of go over this diagnostic workup. It is a class effect of ADCs. I think in the studies with HER3-DXd, the frequency was about 5%. And, you know, this can go up to 15% to 20% with some other ADCs like trastuzumab deruxtecan. So I think it's just something where we definitely need to educate our patients. I think it's challenging with lung cancer when patients already have baseline shortness of breath, cough. But wanting to say if there's any change in your kind of level of symptoms, please let us know so that we can be suspicious and think about this and work this up. And I liked you what said about, same here at MSK, we would definitely call in our pulmonary folks to help us with management.
And I think if the differential is unclear, a bronchoscopy with biopsy, if possible, is always helpful. I think for patients that had symptomatic ILD, I'd be pretty hesitant and would not likely retry for grades 2, 3, and above. But I think for grade 1, if patients are totally asymptomatic, that would be the real question where we don't have great data but a question about whether to re-treat.
Dr. Jänne:
And in the trials, those patients were allowed to be re-treated. Patients that had higher-grade pneumonitis with symptoms, even if they resolved with treatment, were not allowed to be re-treated.
Dr. Yu:
Well, that's all the time we have for today. Thank you for a robust discussion, Dr. Jänne, and thanks for our audience for listening.
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