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For non-small-cell lung cancer (NSCLC) patients without established actionable alterations in genes such as  EGFR  or  ALK , options for targeted therapy remain limited in clinical practice. About 5% of lung adenocarcinoma patients have tumors with  ERBB2  genetic alterations, with even fewer patients harboring  ERBB2  amplification. Currently, clinical trials mainly use IHC, FISH, or mutation testing to identify potential responders to ERBB2-targeting agents. The use of next-generation sequencing (NGS) to detect  ERBB2  alterations, including copy number variants, is rare. In this study, we present an EGFR- and ALK-negative advanced NSCLC case for which we conducted comprehensive tumor genomic profiling to identify potentially actionable alterations. The tumor harbored an  ERBB2  amplification, and trastuzumab-based therapy resulted in an excellent response, with a necrotic regression of the patient's lung lesion. Although he developed brain metastasis four months after trastuzumab initiation, he survived for an additional period of eight months without local recurrence or other systemic metastasis. This case report shows that the use of comprehensive genetic testing enables the identification of rare actionable alterations in NSCLC patients without other options for targeted treatment.

Advanced Lung Adenocarcinoma Patient with ERBB2 Amplification Identified by Comprehensive Genomic Profiling Benefits from Trastuzumab