TDXD is highly emetogenic. Adding low-dose olanzapine to the standard three-drug antiemetic prophylaxis regimen is a transformative strategy that significantly reduces both acute and delayed nausea, making the potent therapy much more tolerable for patients.

Drawing lessons from T-DXD, experts treat newer exatecan-payload ADCs like RDXD as highly emetogenic from the first dose. Instead of a 'wait and see' approach, they recommend aggressive premedication with a triple-drug antiemetic regimen to prevent nausea and maintain quality of life.

In the DESTINY LUNG-02 trial for HER2-mutant NSCLC, the lower 5.4 mg/kg dose of Trastuzumab-Deruxtecan (TDXD) yielded a 51% response rate, compared to 28% for the higher 6.4 mg/kg dose. This paradoxical outcome was driven by significantly higher toxicity, particularly interstitial lung disease (ILD), at the higher dose, which limited patients' ability to stay on treatment.

To manage the acute GI toxicity of T-DXd, a preemptive three-drug antiemetic combination is recommended. Completely preventing nausea and vomiting is crucial not just for comfort, but for mitigating patient anxiety around chemotherapy and ensuring they can remain on this long-term treatment.

Nausea with TDXD is severe enough that the drug is now considered highly emetogenic. The standard of care is a prophylactic three-drug antiemetic regimen (NK1 antagonist, 5HT3 antagonist, and dexamethasone). Waiting for nausea to occur before treating is a clinical error; prevention is paramount.

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.

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.

When managing toxicities from trastuzumab deruxtecan (TDXD) in urothelial cancer, clinicians should refer to established protocols and literature from breast cancer, where experience is more extensive. This cross-disciplinary approach is necessary for managing side effects like nausea, vomiting, and lung disease until more bladder cancer-specific data becomes available.

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.