AstraZeneca and Daiichi Sankyo announced that their antibody-drug conjugate Enhertu (trastuzumabderuxtecan) has achieved a statistically significant and clinically meaningful improvement in progression-free survival in the Phase III DESTINY-Lung04 trial, marking the first time a HER2-targeted therapy has outperformed the global standard of care as a first-line treatment for this cancer subtype.

The trial evaluated Enhertu against the current frontline regimen—chemotherapy combined with pembrolizumab immunotherapy—in adults with unresectable, locally advanced or metastatic non-squamous non-small cell lung cancer carrying HER2 mutations. This subgroup represents roughly 2–4% of NSCLC cases and tends to affect younger patients, often non-smokers, who face a higher risk of brain metastases and poorer outcomes.

Study leaders noted the results support moving Enhertu earlier into the treatment sequence, addressing a longstanding gap since many patients fail to respond adequately to existing frontline immunotherapy-chemotherapy combinations. Daiichi Sankyo’s R&D leadership emphasized that Enhertu was already established as a second-line option for this population, and these findings now point to its potential benefit even earlier in the disease course.

No new safety signals emerged during the trial, with the therapy’s tolerability profile remaining consistent with prior data. The trial, which enrolled 454 patients across sites in Asia, Europe and North America, will continue to track overall survival as a secondary measure. Full data are expected to be presented at an upcoming oncology conference and submitted to regulators worldwide.

Enhertu, jointly developed by the two companies since 2019, is already approved across multiple HER2-driven cancers, including breast, gastric and previously treated lung cancers, in more than 100 countries. This latest result adds to a growing body of evidence supporting the drug’s expansion into earlier lines of therapy.

Written By: Sayan Das 

Graphics by: Pramit Hazra