Case 2: Safety Considerations in the Use of T-DXd for HER2+ mBC



Chau T. Dang, MD:As exciting as fam-trastuzumab deruxtecan is, there’s a toxicity that we have to be aware of: interstitial lung disease, or pneumonitis. In the initial studies, when we weren’t fully aware of this potential toxicity, the incidence rates of all-grade ILDs [interstitial lung diseases]/pneumonitis was about 15%. Unfortunately, we had several deaths. But with the awareness of this toxicity, the rates have come down significantly. In the DESTINY-Breast03 study, the incidence rates were about 10% for all-grade ILD/pneumonitis, and no patients died, which is wonderful. To mitigate this toxicity, we have to be aware and on the lookout. We know a patient may be experiencing pulmonary toxicities by being aware of what the patient is reporting, such as shortness of breath, cough, or a fever. Be on the lookout and quickly get imaging, such as a CT scan of the chest. If there’s any sign of interstitial disease, the drug must be stopped, and we must get our pulmonary colleagues involved to help us manage our patients. Often times, that involves initiating steroids. Being aware is very important. There are guidelines in place for us to follow and monitor our patients.

As far as the TKIs [tyrosine kinase inhibitors], such as tucatinib and neratinib, diarrhea is a toxicity that we’re on the lookout for, and we’re very familiar with managing diarrhea. We’ve learned how to manage diarrhea with neratinib when it was approved first in using a regimen that’s been published by the CONTROL study, using loperamide as our antidiarrheal agent. There are other agents that we can use if optimal loperamide isn’t effective enough. If neratinib is used, there’s that escalation schema that we’ve used to basically manage the diarrhea for patients who are starting out neratinib.

Cardiotoxicity was a big issue 20 years ago. When trastuzumab was approved in 1988, it was a surprise that there was this issue with heart failure, probably because we were unaware and we were giving anthracycline. We had to learn how to do echo monitoring. ILDs are the new surprise. The question that comes up is, how do you monitor for ILD? Do you do PFTs [pulmonary function tests] serially to see if there’s a change in their result to advise on what to do with the drug? It’s an unanswerable question, but it’s a common question.

How do you monitor? You really don’t. You have to be on the lookout, know what can happen, and listen to the patient to see if they have any symptoms of concern, like shortness of breath, cough, fever.

Transcript edited for clarity.

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