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News
A major phase 3 trial shows trastuzumab deruxtecan (T-DXd) nearly doubles progression-free survival compared to standard chemoimmunotherapy in HER2-mutant non-small cell lung cancer. The DESTINY-Lung04 trial reported a median PFS of 14.3 vs. 8.3 months, marking the first phase 3 win for a HER2-directed therapy in this setting. However, no overall survival benefit was observed, and ILD risk was notably higher with T-DXd.
A landmark phase 3 trial has put trastuzumab deruxtecan (T-DXd; ENHERTU) on the map as a potential new first-line standard of care for patients with advanced or metastatic HER2-mutant non-small cell lung cancer (NSCLC). The DESTINY-Lung04 trial, presented at the World Conference on Lung Cancer 2026 in Seoul, enrolled 454 treatment-naive patients and showed T-DXd significantly outperformed pembrolizumab plus platinum-based chemotherapy on progression-free survival — the primary endpoint.
The response rates told a similarly compelling story, with T-DXd achieving a 70% objective response rate vs. 44.5% for chemoimmunotherapy. Researchers noted consistent benefit across key subgroups, including patients with brain or liver metastases and older adults. That said, overall survival data didn't favor T-DXd — a finding researchers attribute partly to more patients in the control arm receiving effective HER2-directed therapies afterward.
By the Numbers:
Why it matters: HER2-mutant NSCLC is a rare but aggressive cancer where standard immunotherapy often falls short. This is the first phase 3 trial to demonstrate superiority of HER2-directed therapy over standard of care upfront, potentially reshaping treatment guidelines for this patient population.
