Trastuzumab deruxtecan improves progression‑free survival versus pembrolizumab in HER2‑mutant NSCLC

First‑line therapy with trastuzumab deruxtecan (T‑DXd) demonstrated a statistically significant improvement in progression‑free survival compared with pembrolizumab combined with platinum‑based chemotherapy in patients with advanced or metastatic HER2‑mutant non‑small cell lung cancer (NSCLC). The primary results of the phase 3 DESTINY‑Lung04 trial were presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC).

The multicenter study enrolled participants whose tumors harbored HER2 mutations and randomized them to receive either T‑DXd or the standard pembrolizumab‑plus‑platinum regimen as initial treatment. Across the cohort, T‑DXd achieved a longer median progression‑free interval, meeting the trial’s primary efficacy endpoint. Safety profiles were consistent with previous reports for both regimens, and no new safety signals emerged. These findings position trastuzumab deruxtecan as a potential new standard of care for HER2‑mutant NSCLC, offering clinicians an evidence‑based alternative to immunotherapy‑based chemotherapy in the first‑line setting.