A real-world-style case report described 23-month progression-free survival after second-line trastuzumab deruxtecan in a patient with HER2-positive metastatic gastroesophageal junction adenocarcinoma. The patient had rapid progression on standard first-line chemoimmunotherapy before receiving the antibody-drug conjugate in the second-line setting, with investigators reporting extended disease control. While a single patient cannot establish efficacy, the durability signal reinforces interest in expanding the sequencing conversation for HER2-positive gastric and gastroesophageal cancers beyond first-line regimens.