First-line trastuzumab deruxtecan (T-DXd) in metastatic HER2-mutant NSCLC: DESTINY-Lung04 primary results

In this OncLive Rapid Readout, Julia Rotow, MD, of Dana-Farber Cancer Institute, reviews primary results from DESTINY-Lung04, the first randomized phase 3 trial of a HER2-directed therapy vs standard of care in the first-line setting for metastatic HER2-mutant non-small cell lung cancer (NSCLC). The trial randomized 454 treatment-naive patients to trastuzumab deruxtecan monotherapy or pembrolizumab plus platinum chemotherapy and pemetrexed. Trastuzumab deruxtecan met the primary endpoint, improving median progression-free survival from 8.3 to 14.3 months (HR, 0.63; P < .0001), with benefit across subgroups including patients with brain metastases and a history of tobacco use. Objective response rate was 70% vs 44.5%, with longer duration of response. Overall survival did not favor trastuzumab deruxtecan at this preliminary analysis, which Rotow attributes to imbalances in subsequent HER2-directed and immunotherapy-based treatment. Interstitial lung disease occurred in about 1 in 5 patients, mostly grade 1 or 2, and requires proactive monitoring and management.