Trastuzumab deruxtecan (TDXD) and datopotamab deruxtecan (Dato-DXd) share the same cytotoxic payload, yet Dato-DXd has a much lower rate of interstitial lung disease (ILD). This indicates the toxicity is driven by the antibody-antigen interaction, not the payload itself.

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.

Interstitial Lung Disease (ILD) is a significant risk with TDXD. However, a history of a completely resolved grade 1 event does not automatically preclude a patient from receiving the drug again. Clinicians may consider a re-challenge, balancing the risk against the lack of other viable therapies.

Given the risk of interstitial lung disease (ILD) with TDXD, clinicians should consider a baseline pulmonology consult for NSCLC patients with pre-existing lung issues. This proactive step helps establish a baseline and can prevent mismanaging potential adverse events.

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.

Adopting T-DXd in early-stage breast cancer requires frequent chest CT scans to monitor for potentially fatal interstitial lung disease (ILD), a practice not standard for current therapies. This presents significant new logistical challenges, including securing insurance approvals, managing patient access, and increasing the overall burden of care.

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.