Tolerability is the sticking point for TROP2-directed antibody-drug conjugates (ADCs) in EGFR-mutated non-small cell lung cancer (NSCLC). Thoracic oncologists debated how to sequence datopotamab deruxtecan (Dato-DXd) and amivantamab after frontline osimertinib, with both options showing activity but distinct toxicity profiles. Skin reactions, stomatitis, and eye-related side effects are shaping real-world treatment decisions more than efficacy data alone.
When frontline osimertinib stops working in EGFR-mutated NSCLC, oncologists are left choosing between two active but imperfect options: the TROP2-directed ADC datopotamab deruxtecan (Dato-DXd) and amivantamab-based regimens. At a recent OncLive Scientific Interchange, experts agreed there's no clear winner — it largely comes down to which side effect profile a patient can tolerate. Amivantamab's dermatologic toxicities are a dealbreaker for some, while Dato-DXd's stomatitis and ocular risks present their own management challenges.
Practical workarounds are emerging: routing dexamethasone mouthwash through hospital pharmacies, using frozen oral mouthpieces during infusions, and not delaying treatment for eye exams unless pre-existing eye disease is present. Meanwhile, newer data on sacituzumab tirumotecan from the phase 3 OptiTROP-Lung04 trial showed improved PFS and OS vs. chemotherapy with no drug-related interstitial lung disease — a potentially meaningful differentiator.
Key Takeaways:
Why it matters: As ADCs become a cornerstone of second-line NSCLC therapy, managing their toxicities — not just their efficacy — will define how broadly they can be used in real-world practice.
