Contrary to the belief that any interstitial lung disease (ILD) requires permanent discontinuation of TDXD, data shows patients with asymptomatic, radiographically-identified Grade 1 ILD can be safely rechallenged. Treatment is paused and the patient is treated, but therapy can resume once resolved. Symptomatic ILD, however, requires permanent discontinuation.

While caution is necessary, a patient's prior history of pneumonitis does not automatically disqualify them from receiving an ADC with a known risk of this side effect. Clinical judgment is key; if the prior event was from a specific, known drug combination and has fully resolved, proceeding with careful monitoring can be a viable option.

For urothelial cancer patients treated with trastuzumab deruxtecan (TDXD), developing symptomatic (Grade 2) interstitial lung disease or pneumonitis is a critical event. Following protocols from other cancers, this requires permanent discontinuation of the therapy. Re-challenging the patient with TDXD after a Grade 2 event is not recommended without more disease-specific safety data.

The discovery of low-grade, asymptomatic interstitial lung disease (ILD) on scans for patients on certain ADCs does not mandate permanent discontinuation. By holding the drug, initiating steroids, and involving pulmonology, the inflammation can resolve, often allowing the patient to safely resume a highly effective therapy.

With ADCs carrying a risk of interstitial lung disease (ILD), a critical safety measure is to act on radiological findings alone. Even if a patient is completely asymptomatic, new ground-glass opacities on a CT scan require an immediate treatment hold to prevent potentially rapid and severe pneumonitis.

To manage the risk of interstitial lung disease (ILD) with TDXD, experts now recommend routine screening with high-resolution chest CT scans every 6-12 weeks. This practice aims to catch asymptomatic, grade 1 ILD early, allowing for treatment holds and steroid intervention, which may preserve the option to rechallenge.

Unlike some immunotherapy guidelines, experts recommend immediate steroid treatment for even Grade 1 (asymptomatic) ADC-induced pneumonitis or interstitial lung disease (ILD) found on scans. This aggressive, proactive approach is considered necessary due to the risk of rapid clinical deterioration, prioritizing safety and the ability to resume cancer therapy.

Despite label warnings against rechallenging trastuzumab deruxtecan (TDXD) after any symptomatic (Grade 2+) interstitial lung disease (ILD), some experts differentiate. For 'soft call' cases with minimal symptoms, they may consider restarting after a transparent patient discussion, believing not all Grade 2 ILDs carry the same risk.

Interstitial lung disease (ILD) is a serious risk with trastuzumab deruxtecan (TDXD). Oncologists must take it extremely seriously, engaging a pulmonologist immediately at the first sign of symptoms or CT scan findings. A collaborative, multidisciplinary approach is essential for safely managing this potentially fatal toxicity.