Case Report: Dramatic response of trastuzumab rezetecan in an NSCLC patient with EGFR sensitive mutation and primary ERBB2 genetic alterations.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have provided significant clinical benefit to patients with EGFR-mutant non-small cell lung cancer (NSCLC), but multiple concurrent genetic alterations may limit their efficacy. We report a case of advanced lung adenocarcinoma harboring concurrent EGFR exon 19 deletion, ERBB2 amplification, and ERBB2 p.S310F mutation. The patient experienced disease progression after multiple lines of therapy, including osimertinib-based treatment, pemetrexed/carboplatin plus ivonescimab, and nab-paclitaxel plus Endostar. Considering that primary ERBB2 genetic alterations might contribute to the limited benefit from EGFR-TKI-based therapy, the patient subsequently received trastuzumab rezetecan monotherapy. After four cycles of treatment, the patient achieved a partial response in pulmonary lesions and a complete response in intracranial metastases. This case indicates that trastuzumab rezetecan may be a promising treatment option for EGFR-mutant NSCLC with concurrent ERBB2 genetic alterations, even after failure of multiple lines of treatment.