May 11, 2026
Post-TTLC 2026: Dr. Doroshow opens with a question on the role of antibody-drug conjugates (ADCs) in EGFR-mutated lung disease, asking what it would take for Dr. Patel to consider a first- or second-line datopotamab deruxtecan (Dato-DXd) plus osimertinib approach. Dr. Patel describes Dato-DXd as a TROP2-directed ADC with FDA approval in refractory EGFR-mutated non-small cell lung cancer (NSCLC). He uses it second line after FLAURA2 or MARIPOSA, and typically third line after osimertinib monotherapy followed by MARIPOSA-2 (chemotherapy plus amivantamab). He is interested in moving Dato-DXd earlier with osimertinib based on preliminary efficacy and CNS-protective signals, but flags ADC chemotherapy-like toxicities — stomatitis, low-rate interstitial lung disease, dry eye, cytopenias, and alopecia.
Dr. Doroshow says Dato-DXd is a definite option but acknowledges the response rate is somewhat underwhelming, and as an early-phase trialist she is always looking for clinical trial alternatives. She is cautious about moving Dato-DXd upfront pending more data given mucositis severity. Dr. Patel highlights newer linker chemistries that improve payload delivery, biparatopic bindings for greater specificity, and higher drug-to-antibody ratios (DARs). He acknowledges a paradox: ADCs are positioned as precision-guided chemotherapy, yet diagnostics for selecting them, outside HER2, remain limited.
On managing Dato-DXd stomatitis, Dr. Patel uses dexamethasone steroid mouthwashes started early. Dr. Doroshow agrees but notes compounded dexamethasone mouthwash is not available at every pharmacy. She uses oral cryotherapy during infusion, including a creative patient adaptation of putting ice in a sandwich bag, and reports good prevention of mucositis.
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