The Use of Fam‐Trastuzumab Deruxtecan‐nxki in Treating ERBB2 Amplified Small Cell Lung Cancer Transformed From Non‐Small Cell Lung Cancer: A Case Report

Histological transformation from non‐small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is a recognized mechanism of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), leading to poor prognosis and significant therapeutic challenges. We present a case of a 66‐year‐old female with de novo metastatic NSCLC harboring an EGFR mutation, RET rearrangement, and ERBB2 amplification, who experienced transformation to SCLC while on osimertinib. Subsequently, she exhibited primary refractory disease to both first‐line platinum doublet with immunotherapy and second‐line lurbinectedin. Given her transformed disease and continued ERBB2 amplification on next‐generation sequencing (NGS), the patient was initiated on trastuzumab deruxtecan (T‐DXd) at a dosage of 5.4 mg/kg intravenously every 3 weeks. The patient had minimal side effects and obtained a partial response with a progression‐free survival (PFS) of 13.1 months, better than historically poor prognosis seen in transformed SCLC. This case underscores the potential role of human epidermal growth factor receptor 2 (HER‐2) directed therapies, such as T‐DXd, in transformed SCLC.