Strategies for Monitoring and Managing T-DXd-Related Adverse Effects
Panelists discussed the persistent risk of interstitial lung disease with trastuzumab deruxtecan, emphasizing the need for early detection through routine imaging, rapid intervention to prevent severe toxicity, and cautious retreatment in select cases where interstitial lung disease was mild and well managed.
The panel shifted focus to the safety profile of trastuzumab deruxtecan (T-DXd), particularly interstitial lung disease (ILD), which remains a significant concern despite increased vigilance. Imaging practices have evolved in response to previous studies, with many clinicians now scanning every 9 weeks to detect early, asymptomatic ILD before it progresses. The discussion emphasized that once ILD reaches grade 2 or higher, treatment with T-DXd typically must be permanently discontinued, highlighting the importance of catching it early. Even with improved monitoring protocols, cases of fatal ILD continue to be reported, reinforcing the need for both clinician awareness and patient education.
Further insights were shared into 2 fatal ILD cases from the recent trial, both occurring outside the US. In one instance, the patient declined treatment after diagnosis, while in the other, delayed diagnosis due to uncertainty between ILD and infection led to suboptimal management. These examples illustrate the critical need for rapid evaluation and intervention. There was also mention of a slightly elevated rate of cardiac dysfunction in the same trial, an unexpected finding that has yet to be fully understood and will require further review once more data are available.
The conversation also covered the topic of T-DXd retreatment after ILD, referencing real-world data that suggested patients who experienced grade 1 ILD could safely resume therapy. Although the dataset was small, the reintroduction of the drug appeared to offer renewed clinical benefit, which could be relevant in scenarios where T-DXd is used early in the treatment sequence. This reinforces the need for meticulous monitoring to catch ILD early, particularly during periods when respiratory infections are common. The group acknowledged the complex radiographic presentation of ILD, which can mimic infection, making accurate diagnosis and early steroid intervention essential to preserving future treatment options.
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