Dr Halmos on the FDA Approval of Dato-DXd for Advanced/Metastatic EGFR-Mutated NSCLC

“For EGFR-mutated lung cancer, after targeted [therapy] and chemotherapy, [Dato-DXd]has even more activity, [including a] 45% response rate [and a] 6.5-month duration of response, with a reasonable [safety profile].”

Balazs Halmos, MD, associate director of Clinical Science at the Montefiore Einstein Comprehensive Cancer Center, as well as a professor in the Department of Oncology (Medical Oncology) and the Department of Medicine (Oncology & Hematology) at the Albert Einstein College of Medicine, discussed the FDA’s accelerated approval of datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) for the treatment of adult patients with previously treated, locally advanced or metastatic, EGFR-mutated non–small cell lung cancer (NSCLC).

On June 23, 2025, the FDA granted accelerated approval to Dato-DXd for this indication based on pooled findings from the phase 2 TROPION-Lung05 (NCT04484142) and phase 3 TROPION-Lung01 (NCT04656652) trials. Among 114 patients with EGFR-mutated NSCLC who had received prior EGFR-directed therapy and platinum-based chemotherapy, treatment with Dato-DXd resulted in an overall response rate of 45% (95% CI, 35%-54%) and a median duration of response of 6.5 months (95% CI, 4.2-8.4).

Dato-DXd is administered at a recommended dose of 6 mg/kg, up to a maximum of 540 mg in patients weighing 90 kg or more, once every 3 weeks until disease progression or unacceptable toxicity. Prescribing information includes warnings for interstitial lung disease/pneumonitis, ocular adverse effects (AEs), stomatitis, and embryo-fetal toxicity.

According to Halmos, this regulatory milestone offers a new therapeutic option for patients with EGFR-mutated NSCLC who have progressed on targeted therapies and chemotherapy, a population for whom available treatments remain limited. He noted that although the Dato-DXd arm did not meet the primary overall survival end point in the broader TROPION-Lung01 population, subgroup analyses revealed more pronounced activity in patients with EGFR-mutated disease, supporting its indication in this setting.

Halmos emphasized that although comparative data between Dato-DXd and other post-platinum regimens, such as docetaxel, remain unavailable, the agent provides a meaningful addition to the EGFR-mutated NSCLC treatment sequence. He highlighted the need for careful management of AEs, particularly mucositis, and noted ongoing efforts to optimize supportive care strategies.