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Trastuzumab Deruxtecan Outperforms Standard Chemo in HER2-Mutant NSCLC

Patients with advanced HER2-mutant non-small cell lung cancer saw a significant extension in progression-free survival when treated with trastuzumab deruxtecan rather than standard immunotherapy combined with chemotherapy. The primary findings from the global Phase 3 DESTINY-Lung04 trial were unveiled at the 2026 World Conference on Lung Cancer in Seoul.

Trastuzumab Deruxtecan Outperforms Standard Chemo in HER2-Mutant NSCLC
Photo: Bio & News

The study tracked 454 treatment-naive patients with unresectable or metastatic disease. Those receiving the drug, known as T-DXd, achieved a median progression-free survival of 14.3 months, compared to 8.3 months for the group treated with pembrolizumab and platinum-based chemotherapy. Dr. Julia Rotow of the Dana-Farber Cancer Institute noted that the results offer a potential shift in the first-line treatment landscape for this aggressive cancer subtype, which has historically shown limited response to conventional immunotherapy.

Beyond survival metrics, T-DXd demonstrated a superior objective response rate of 70%, versus 44.5% in the control arm. While the trial indicated a median overall survival of 29.3 months for T-DXd against 33.1 months for the control group, investigators cautioned that these figures were influenced by an imbalance in subsequent treatments received by patients after the study intervention. Regarding safety, drug-related interstitial lung disease occurred in 20.8% of the T-DXd group, primarily at lower grades, while serious adverse events were comparable between both cohorts at approximately 34%.

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