ArticleFrontiers in oncology2026
HER2 amplification as a resistance mechanism to osimertinib and its successful treatment with trastuzumab deruxtecan: a case report.
Article in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Acquired resistance to osimertinib in EGFR-mutant advanced non-small cell lung cancer is inevitable, and management following progression remains an evolving clinical challenge. HER2 amplification is a recognised but underreported off-target resistance mechanism, and its optimal management is not yet established. Trastuzumab deruxtecan has shown activity in HER2-altered NSCLC, but real-world data describing its use in this specific resistance context, particularly with respect to intracranial activity, remain scarce. We report the case of a 50-year-old man with metastatic NSCLC harbouring an EGFR exon 19 deletion who experienced disease progression through multiple lines of therapy, including 3 years of first-line osimertinib, platinum-based chemotherapy, atezolizumab-bevacizumab-paclitaxel-carboplatin, and repeated radiotherapy for intracranial metastases. Comprehensive genomic profiling at progression identified acquired HER2 (ERBB2) amplification, confirmed by immunohistochemistry (IHC 3+) and fluorescence
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