Modern antibody-drug conjugates (ADCs) like trastuzumab deruxtecan can kill nearby cancer cells that don't express the target protein. This 'bystander effect' is a game-changer, allowing ADCs to be effective even in tumors with varied (heterogeneous) protein expression, which has historically been a major clinical challenge.
The standard HER2 tests were developed to identify HER2-positive tumors, not to precisely quantify low levels of expression. This creates a diagnostic challenge for identifying patients eligible for HER2-low targeted ADCs, requiring closer collaboration with pathology to interpret results that may be near the threshold, such as HER2-zero but with some minimal staining.
When monitoring for cardiac toxicity with ADCs, assessing myocardial 'strain' via echocardiogram provides an earlier warning sign than ejection fraction (EF) alone. A change in strain, which measures the function of small muscle fibers, often precedes a drop in the overall EF, allowing for earlier intervention.
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.
To proactively screen for interstitial lung disease (ILD), a serious risk with trastuzumab deruxtecan (TDXD), imaging should be conducted more frequently than the typical 12-week interval. The recommended strategy is to scan patients every nine weeks, or after every three cycles, to identify asymptomatic Grade 1 ILD cases early.
For required ocular monitoring with certain ADCs, patients do not need to see a specialist ophthalmologist. An optometrist, including those at accessible and lower-cost retail locations, is fully qualified to perform the necessary exams. This practical tip helps mitigate financial toxicity and improves patient access to care.
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.
When choosing between TROP2-directed ADCs like sacituzumab govitecan and datopotamab deruxtecan, the decision often hinges on side effect profiles and scheduling convenience, not superior efficacy. Datopotamab has more oral/ocular issues but is given every three weeks, while sacituzumab causes more neutropenia and requires visits two out of every three weeks.
Clinicians should be aware of 'overflow diarrhea,' a paradoxical symptom where a patient is severely constipated with a hard stool impaction, but liquid stool flows around it. Misdiagnosing this as diarrhea and administering anti-diarrheals like loperamide can worsen the underlying constipation and cause significant harm. A thorough history and assessment are critical.
For patients at high risk of developing interstitial lung disease (ILD) or those who may underreport symptoms, providing a pulse oximeter for home monitoring is a proactive safety measure. This allows for early detection of oxygen desaturation, a critical sign of pneumonitis, enabling prompt intervention before symptoms become severe.
A simple and effective way to explain antibody-drug conjugates (ADCs) to patients is the 'package of mail' analogy. The antibody is the address label directing the therapy to the cancer cell (the house), and the chemotherapy 'payload' is the package itself, which is delivered and opened inside to kill the cell.