Dr Passaro on the Significance of the TROPION-Lung05 Trial of Dato-DXd in NSCLC

Antonio Passaro, MD, PhD, medical oncologist, Division of Thoracic Oncology, European Institute of Oncology, discusses the significance of data from the phase 2 TROPION-Lung05 trial (NCT04484142) of datopotamab deruxtecan (Dato-DXd; DS-1062a) in patients with non–small cell lung cancer (NSCLC).

A significant focus of the 2023 ESMO Congress was the emerging class of antibody-drug conjugates (ADCs), which continues to show promise for the treatment of patients with NSCLC, Passaro begins. One such study presented at the meeting was TROPION-Lung05. This global, open-label study included patients with advanced/metastatic NSCLC with documented actionable genomic alterations (AGAs), such as EGFR, ALK, ROS1, NTRK, BRAF, RET, or MET exon 14 skipping mutations, he details. Patients also needed to have disease progression on or after at least 1 AGA-specific therapy and platinum-based chemotherapy. A total of 137 patients were treated on the study, with the majority having undergone multiple prior lines of therapy. Notably, over half of the participants displayed EGFR mutations.

Results showed promising antitumor activity with Dato-DXd in this patient population, Passaro reports. The agent produced a confirmed overall response rate of 35.8% (95% CI, 27.8%-44.4%) and a disease control rate of 78.8% (95% CI, 71.0%-85.3%). Moreover, the median duration of response was 7.0 months (95% CI, 4.2-9.8). These outcomes were observed in the overall population, including patients with EGFR mutations.

The safety profile of Dato-DXd was also assessed, with the most common grade 3 or higher treatment-emergent adverse effects (AEs) being stomatitis, anemia, decreased appetite, and fatigue. Other common AEs included mucositis and ocular toxicity, Passaro details. Notably, not all patients experienced these toxicities, indicating individual variability in treatment response and the development of toxicities, he adds.

These findings indicate the potential for Dato-DXd to provide clinical benefit and expand the currently limited treatment armamentarium for patients with advanced/metastatic NSCLC and AGAs who have progressed on prior therapy. Further research and clinical trials are needed to confirm these findings and better understand the safety and efficacy of ADCs in NSCLC, especially in the context of evolving resistance mechanisms, Passaro concludes.