Datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) has been approved for patients with EGFR‑mutated non–small cell lung cancer (NSCLC) who previously received EGFR‑directed therapy and platinum‑based chemotherapy. Following the approval, a panel of thoracic oncologists, nurse practitioners and pharmacists convened by CancerNetwork® reviewed the drug’s efficacy, safety and potential place in treatment sequencing.
Panelists noted that data from the phase 2 TROPION‑Lung05 trial support Dato‑DXd as more effective and better tolerated than docetaxel for this population. Common toxicities highlighted included stomatitis and interstitial lung disease (ILD)/pneumonitis. Clinicians drew on experience with other antibody‑drug conjugates to emphasize the importance of early prevention for stomatitis, recommending prophylactic steroid mouthwashes and noting mixed evidence for cryotherapy or ice chips once stomatitis develops. Timely access to dexamethasone mouth rinse was identified as a practical barrier in some community pharmacies.
ILD risk was underscored as a particular concern in a lung cancer population, but panelists observed that rates were not dramatically higher than those seen with ADCs in breast cancer. Eye toxicities were also discussed; steroid eye drops can be started empirically, but prompt ophthalmology evaluation is advised when symptoms arise. Panelists stressed the need for patient education and coordination across oncology, pharmacy and ophthalmology teams to manage adverse events.
Experts recommended obtaining molecular profiling at progression to guide sequencing. MET amplification appeared to be associated with lower response to Dato‑DXd, prompting consideration of MET‑directed therapies when present. Choices between Dato‑DXd, amivantamab (with or without chemotherapy) and platinum‑doublet chemotherapy varied by prior therapy (for example, osimertinib alone versus osimertinib plus chemotherapy), the patient’s progression‑free survival on prior regimens, disease burden, central nervous system involvement and histology. Several panelists favored using platinum‑doublet chemotherapy before Dato‑DXd in some settings and reserving Dato‑DXd for later lines, while others would consider it earlier for specific presentations such as squamous histology with EGFR mutation or limited extracranial disease.
Cardiac safety concerns that affect some ADCs were not raised for Dato‑DXd by the panel. Panelists called for more comparative data and improved patient‑reported quality‑of‑life measures to better define Dato‑DXd’s role relative to other available options and to help patients and clinicians weigh efficacy against toxicity in shared decision‑making.
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