A Pooled Analysis of Datopotamab Deruxtecan in Patients With EGFR-Mutated NSCLC

Abstract

Background: This exploratory analysis assessed datopotamab deruxtecan (Dato-DXd) in pretreated patients with advanced or metastatic NSCLC and EGFR mutations. Methods: Data were pooled from the phase II TROPION-Lung05 (NCT04484142) and phase III TROPION-Lung01 (NCT04656652) trials. Patients with EGFR-mutated advanced or metastatic NSCLC, who had received previous targeted therapies and platinum-based chemotherapy, received Dato-DXd 6 mg/kg (TROPION-Lung05) or were randomized to Dato-DXd 6 mg/kg or docetaxel 75 mg/m2 (TROPION-Lung01) once every 3 weeks. End points included objective response rate, duration of response, and progression-free survival, all per blinded independent central review, overall survival, and safety. Results: In total, 117 patients with EGFR mutations who received Dato-DXd were included in the pool. The population was heavily pretreated (median three lines of previous therapies; range, 1-5) and predominantly Asian (69%). The most common mutations were exon 19 deletion (51%), L858R (32%), and T790M (27%); more than one EGFR mutation could be present. The confirmed objective response rate was 43% (95% confidence interval [CI]: 34-52), including five complete responses (4%). Median duration of response was 7.0 months (95% CI: 4.2-9.8). Median progression-free survival and overall survival were 5.8 (95% CI: 5.4-8.2) and 15.6 months (95% CI: 13.1-19.0), respectively. The safety profile of Dato-DXd was consistent with the individual studies. No new safety signals were observed. Rates of grade greater than or equal to 3 treatment-related adverse events and serious adverse events were 23% and 6%, respectively. Conclusion: Dato-DXd demonstrated meaningful clinical activity in patients with EGFR-mutated advanced or metastatic NSCLC who had progressed on EGFR-directed therapies and chemotherapy, with an acceptable safety profile. (c) 2025 The Authors. Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).